Atherogenic lipoprotein phenotype and LDL size and subclasses in patients with peripheral arterial disease

The type of dyslipidemia in patients with peripheral arterial disease (PAD) is still ill defined. PAD patients often show elevated triglycerides and reduced HDL-cholesterol, two lipid abnormalities usually accompanied by decreased LDL size in the "atherogenic lipoprotein phenotype" (ALP). We investigated (1) whether PAD patients have lower LDL size, (2) altered LDL subclass distribution and (3) the prevalence of ALP. We measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis in 31 adults with intermittent claudication and 31 age-BMI-matched controls. Patients had higher prevalence of hypertension (p=.0132), smoking (p<.0020) and diabetes (p=.0024), with lower HDL-cholesterol (p<.0001) and increased triglycerides (p=.0057); LDL size was smaller (p<.0001), with decreased larger subclasses (LDL-I, p<.0001; LDL-IIA, p=.0068) and increased smaller particles (LDL-IIIA, p<.0001; LDL-IIIB, p=.0013; LDL-IVA, p=.0029; LDL-IVB, p<.0001). The presence of PAD was independently associated with smoking (OR 7.2, p=.0099), hypertension (OR 6.5, p=.0362), diabetes (OR 5.5, p=.0450) and elevated small, dense LDL (OR 6.7, p=.0497). The concomitant presence of high triglycerides, low HDL-cholesterol and elevated small, dense LDL in patients was 26% (versus 0% controls, p=.0024). ALP seems to characterize PAD dyslipidemia, but prospective studies are needed to test whether this lipoprotein phenotype may represent a risk factor too.     

Influence of physical mobility and season on 25-hydroxyvitamin D-parathyroid hormone interaction and bone remodelling in the elderly

OBJECTIVE: To investigate influences of physical mobility and season on 25-hydroxyvitamin D-intact parathyroid hormone (iPTH) interaction in the elderly. DESIGN: We examined 188 frail institutionalized elderly at the expected nadir of their serum vitamin D concentrations (winter). This group was compared with 309 healthy ambulatory elderly at the expected time of maximum vitamin D repletion (summer), to accentuate the influences of season and physical activity. METHODS: Serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, iPTH and urinary deoxypyridinoline (DPD) were measured. RESULTS: Vitamin D metabolites were significantly lower in the institutionalized elderly (P<0.0001), with an 82.5% prevalence of vitamin D deficiency (25-hydroxyvitamin D <12ng/ml) in institutionalized elderly in wintertime and 15.5% in ambulatory elderly in summertime. Overall, median iPTH did not differ between groups. However, median iPTH secretion in the presence of low vitamin D serum concentrations (5-30ng/ml) was greater in ambulatory elderly. This could be explained by lower mobility status being correlated with greater serum calcium concentrations (r=0.24, P=0.02 in women; r=0.35, P=0. 001 in men) and greater urinary excretion of DPD (r=0.41, P=0.0001 in women; r=0.42, P=0.0002 in men), independent of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and iPTH. CONCLUSIONS: These data support the hypothesis that immobility, even in the presence of vitamin D deficiency, acts as an overriding influence on bone metabolism by promoting bone resorption (measured as urinary DPD) and increasing serum calcium independent of iPTH. Therefore mobility status may substantially affect 25-hydroxyvitamin D threshold values and the degree to which patients benefit from vitamin supplementation.     

Knowledge and attitudes regarding cardiovascular disease risk and prevention in patients with coronary or peripheral arterial disease

BACKGROUND: We compared perceptions regarding risk of cardiovascular events and benefits of cardiovascular disease (CVD) risk factor reduction between patients with peripheral arterial disease (PAD), patients with coronary artery disease (CAD), and patients without atherosclerosis (no disease). METHODS: Participants with no disease (n = 142) had a normal ankle-brachial index and no clinically evident atherosclerosis (group 1). The PAD participants (n = 136) had an ankle-brachial index less than 0.90 and no other clinically evident atherosclerosis (group 2). Participants with CAD (n = 70) had a normal ankle-brachial index and a history of heart disease (group 3). Participants were interviewed regarding risk of mortality, CVD, and the importance of CVD risk factor reduction for hypothetical patients with PAD and CAD. RESULTS: All groups reported that risks of myocardial infarction, stroke, and death were higher for a patient with CAD than for a patient with PAD. Group 2 was less likely than group 3 to believe that PAD is associated with an extremely high risk of stroke (13.3% vs 28.7%; P =.005) or mortality (10.9% vs 26.6%; P =.003). Group 2 was less likely than group 1 to believe that a patient with PAD has a very high risk of myocardial infarction (13.1% vs 23.8%; P =.02), stroke (13.3% vs 27.5%; P =.003), or mortality (10.9% vs 24.3%; P =.004). Compared with group 3, a smaller percentage of patients in group 2 reported that cholesterol lowering was very important in PAD (57.5% vs 75.8%; P =.005). CONCLUSIONS: Compared with other patients, those with PAD underestimated the high risk of cardiovascular events associated with PAD and the benefits of cholesterol-lowering therapy. These findings may help explain the low rates of CVD risk factor control previously reported in patients with PAD.     

Sex differences in peripheral arterial disease: leg symptoms and physical functioning

OBJECTIVES: To compare lower extremity functioning and leg symptoms between women and men with peripheral arterial disease (PAD). DESIGN: Cross-sectional. SETTING: Three Chicago-area medical centers. PARTICIPANTS: One hundred eighty-seven women and 273 men with PAD identified consecutively in patients in the noninvasive vascular laboratories and a general medicine practice at the three medical centers. MEASUREMENTS: Walking speed, 6-minute walk, accelerometer-measured 7-day physical activity, and a summary performance score. The summary performance score combines data on walking velocity, time for five repeated chair rises, and standing balance to achieve a score on a 0 to 12 scale (12 = best). RESULTS: Women with PAD were older and had a lower prevalence of prior leg revascularization, a higher prevalence of spinal stenosis, and a lower prevalence of other cardiovascular disease than men with PAD. Mean ankle brachial index (ABI) values +/- standard deviation were similar in women and men with PAD (0.64 +/- 0.15 vs 0.66 +/- 0.14, P =.15). Women with PAD were significantly more likely than men with PAD to have exertional leg pain that sometimes begins at rest (27.8% vs 13.2%, P <.001). Women with PAD had slower walking speed (0.81 vs 0.92 m/s, P <.001), shorter 6-minute walk distance (1,047 vs 1,182 feet, P <.001), and a poorer summary performance score (8.9 vs 9.8, P <.001) than men with PAD, adjusting for age, race, height, comorbid disease, and leg symptoms. After adjusting for leg strength, sex differences in 6-minute walk performance and summary performance score were attenuated modestly (1,089 vs 1,177 feet for 6-minute walk, P =.022 and 9.2 vs 9.8 for summary performance score, P =.027). CONCLUSION: Women with PAD had a higher prevalence of leg pain on exertion and rest, poorer functioning, and greater walking impairment from leg symptoms than men with PAD. A higher prevalence of spinal stenosis in women may explain the observed sex differences in leg symptoms. Poorer leg strength in women may contribute to poorer lower extremity functioning in women with PAD than in men with PAD.     

De novo CD5+ diffuse large B-cell lymphoma: a clinicopathologic study of 109 patients.

De novo CD5+ diffuse large B-cell lymphoma (CD5+ DLBCL) is known to have phenotypically and genotypically different characteristics than CD5- DLBCL and mantle cell lymphoma (MCL). To further characterize CD5+ DLBCL, 109 patients with CD5+ DLBCL were reviewed, and the results were compared with those of 384 CD5- DLBCL and 128 cyclin D1+ MCL patients. Patients with CD5+ DLBCL showed a higher age distribution (median, 66 years; P =.0083) and a female predominance (male-female ratio, 49:60, P =.011) compared with those with CD5- DLBCL. CD5+ DLBCL was more closely associated with many aggressive clinical features or parameters than CD5- DLBCL: 69% older than 60 years (P =.039), 34% with performance status greater than 1 (P =.0016), 69% with serum lactate dehydrogenase level higher than normal (P <.0001), 62% with stage III/IV disease at diagnosis (P =.0023), 35% with more than one extranodal site (P =.023), and 40% with B symptoms (P =.0031). The overall International Prognostic Index score was thus significantly higher for the patients with CD5+ DLBCL than for those with CD5- DLBCL (P =.00005). The most frequent site of extranodal involvement was bone marrow (28%), a higher frequency than that for CD5- DLBCL (P <.0001) but lower than that for cyclin D1+ MCL (P =.0015). Histopathologically, CD5+ DLBCL showed centroblastic morphology except for 3 patients with immunoblastic disease, and interfollicular growth pattern (7%) and intravascular or intrasinusoidal infiltration (19%) were observed. Immunophenotypically, CD5+ DLBCL was characterized by a CD5+CD10-CD19+CD20+CD21-CD23- cyclin D1- phenotype and a predominance of surface IgMkappa. Of particular interest is that CD5+ DLBCL was characterized by a survival curve significantly inferior to that for patients with CD5- DLBCL (P =.0026). These findings suggest that CD5+ DLBCL may constitute a unique subgroup of DLBCL.     

Hypovitaminosis D in obese children and adolescents: relationship with adiposity, insulin sensitivity, ethnicity, and season

Low 25-hydroxyvitamin D (25[OH] D) results in hyperparathyroidism and is among the endocrine derangements of adult obesity. There are differing recommendations on defining low 25(OH) D: hypovitaminosis D (serum 25[OH] D concentration <75 nmol/L) and vitamin D deficiency (serum 25[OH] D concentration <50 nmol/L). We sought to evaluate the prevalence of low levels of 25(OH) D by examining hypovitaminosis D (<75 nmol/L), vitamin D sufficiency (> or =75 nmol/L), vitamin D insufficiency (50-74.9 nmol/L), and vitamin D deficiency (<50 nmol/L) in pediatric obesity and the relationship to other calciotropic hormones and adiposity. Serum 25(OH) D, intact parathyroid hormone (iPTH), ionized calcium, glucose, and insulin levels along with hemoglobin A(1c) (HbA(1c)) and quantitative insulin sensitivity check index (QUICKI) were determined in 127 subjects aged 13.0 +/- 3.0 years (49 Caucasian [C], 39 Hispanic [H], and 39 African American [AA]; 61.2% female; body mass index 36.4 +/- 8.1 kg/m(2)) during fall/winter (F/W) and spring/summer (S/S). Body composition was determined by bioelectrical impedance. Hypovitaminosis D was present in 74% of the cohort, but was more prevalent in the H (76.9%, P < .05) and AA (87.2%, P < .05) groups than in the C group (59.1%). Hypovitaminosis D corresponded to decreased vitamin D intake (P < .005) and was more prevalent in F/W than S/S (98.4% vs 49.2, P < .01). Vitamin D deficiency was identified in 32.3% of the entire cohort and was more prevalent in the H (43.6%, P < .0001) and AA (48.7%, P < .0001) groups than in the C group (10.2%) associated with decreased vitamin D intake (P < .0001). Vitamin D insufficiency was present in 41.7% of the cohort, with similar prevalence among C (48.9%), H (33.3%), and AA (38.5%). Vitamin D insufficiency corresponded to decreased vitamin D intake (P < .005), with similar prevalence in F/W and S/S (45.3% vs 38.1%), whereas vitamin D deficiency was not only accompanied by decreased vitamin D intake (P < .0001) but was more prevalent in F/W than S/S (53.1% vs 11.1%, P < .0001). Serum 25(OH) D and iPTH (r = -0.41, P < .0001) levels were negatively correlated without seasonal and ethnic/racial influences. Hypovitaminosis D and vitamin D-deficient groups had higher body mass index, fat mass (FM), and iPTH, but had lower QUICKI than vitamin D-sufficient group (P < .01). Whereas FM was negatively correlated with 25(OH) D (r = -0.40, P < .0001), it was positively correlated with iPTH (r = 0.46, P < .0001) without seasonal and racial/ethnic influences. Serum 25(OH) D was also positively correlated with QUICKI (r = 0.24, P < .01), but was inversely correlated with HbA(1c) (r = -0.23, P < .01). Hypovitaminosis D was identified in 74% of obese subjects, whereas vitamin D deficiency was observed in 32.3% of our cohort. Vitamin D status was influenced by vitamin D intake, season, ethnicity/race, and adiposity. Interrelationships between 25(OH) D, iPTH, and FM were not influenced by season and race/ethnicity. Furthermore, serum 25(OH) D was positively correlated with insulin sensitivity, which was FM mediated, but negatively correlated with HbA(1c), implying that obese children and adolescents with low vitamin D status may be at increased risk of developing impaired glucose metabolism independent of body adiposity. Additional studies are needed to evaluate the underlying mechanisms.     

Impact of oxidative stress on arterial elasticity in patients with atherosclerosis

BACKGROUND: Alterations in the elastic behavior of arteries is an early sign of vascular damage in atherogenesis and may be promoted by oxidative stress (OxS). However, studies designed for simultaneous assessment of arterial elasticity and OxS status in patients with peripheral arterial disease (PAD) are absent. The purpose of this study was to assess large (C1) and small artery elasticity (C2) and indices of OxS in patients with PAD as well as to investigate possible relationships between these parameters. METHODS: Arterial elasticity was assessed noninvasively by pulse wave analysis (PWA) and biochemical measurements were taken from 38 patients with PAD and from 28 matched control subjects. The elasticity indices of the arteries were derived from PWA based on the modified Windkessel model and the OxS status was measured using urinary 8-iso-prostaglandin F2alpha (F2-IsoPs) and plasma baseline diene conjugates of low-density lipoproteins (LDL-BDC). RESULTS: Patients with PAD showed significantly reduced C1 and C2 and increased values of F2-IsoPs and LDL-BDC. There was an inverse association between C1 and F2-IsoPs, as well as between C2 and F2-IsoPs (R=-.3, P=.04; R=-.49, P=.002, respectively) in the patient group, but not in the controls. After controlling for potential confounders in a multiple regression model, the associations between C2 and F2-IsoPs remained significant in the patient group (P<.001). CONCLUSIONS: The possible link between arterial elasticity and F2-IsoPs in patients with PAD suggests that oxidative modifications may be involved in alterations of arterial elastic properties in atherosclerosis.     

Precise quantification of minimal residual disease at day 29 allows identification of children with acute lymphoblastic leukemia and an excellent outcome

The postinduction level of minimal residual disease (MRD) was quantified with a competitive polymerase chain reaction (PCR) technique in 104 children with acute lymphoblastic leukemia (ALL) diagnosed between June 1993 and January 1998 and followed for a median of 4.2 years. A significant correlation was found between the MRD level on day 15 (D15) and day 29 (D29) after the start of induction therapy (r(s) = 0.70, P <.0001). The 15 patients with T-cell disease had higher D29 MRD than those with B-lineage ALL (P =.01). Age was positively related to D29 MRD (r(s) = 0.32, P =.001). The 16 patients who had a relapse had higher D15 and D29 MRD levels than the patients who stayed in remission (median levels D15, 1% versus 0.1%, P =.03; D29, 0.4% versus 0.01%, P =.0001). No patients with a MRD level less than 0.01% on D29 have so far had a relapse, whereas the 7-year probability of event-free survival for patients with higher MRD levels was 0.52 (P =.0007). The group of patients with a D29 MRD less than 0.01% included patients with T-cell disease, white blood cell count more than 50 x 10(9)/L at diagnosis, or age 10 years or older, and could not be identified by up-front criteria. The best-fit Cox model to predict the risk of relapse included D29 MRD (P =.004) and age (P =.009). These findings indicate that with the present treatment protocol MRD quantification at an early stage of therapy identifies patients with a very low risk of relapse. Further trials are needed to reveal whether such patients with D29 MRD less than 0.01% can be cured with less intensive chemotherapy, which would reduce the risk of serious late effects as well as the costs of therapy.     

Peripheral arterial disease in African Americans: clinical characteristics, leg symptoms, and lower extremity functioning

OBJECTIVES: The describe peripheral arterial disease (PAD) in African Americans, and compare findings in African Americans and whites with PAD. DESIGN: Cross-sectional. SETTING: Three academic medical centers. PARTICIPANTS: Three hundred sixty-six whites and 76 African Americans with PAD (as defined by an ankle brachial index (ABI) <0.90) aged 55 and older identified from lower extremity arterial studies performed between 1996 and the fall of 1999. MEASUREMENTS: Comprehensive medical interview, body mass index, and neuropathy score. Functional measurements included the 6-minute walk distance, 4-m walking velocity, and the summary performance score. RESULTS: Age- and sex-adjusted results showed that African Americans had a lower mean ABI than whites (0.60 vs 0.66, P=.001), were less likely to be college graduates (13.7% vs 44.4%, P<.001), and had nearly twice the prevalence of diabetes mellitus (46.8% vs 28.0%, P=.001). After adjusting for age, sex, education level, and ABI, African Americans had a higher prevalence of no exertional leg pain (28.0% vs 18.2%, P=.044) and leg pain with exertion and rest (30.0% vs 17.3%, P=.023). African Americans had a shorter 6-minute walk distance (989 vs 1,156 ft, P<.001), a slower normal-pace 4-m walking velocity (0.79 vs 0.89 m/s, P<.001), a slower fast-pace 4-m walking velocity (1.12 vs 1.20 m/s, P=.012), and a lower summary performance score (8.8 vs 9.6, P=.018) than whites. These differences in functioning were attenuated after adjusting for age, sex, ABI, education, and leg symptoms. CONCLUSION: Poorer lower extremity functioning in African Americans was largely explained by differences in leg symptoms and, to a somewhat lesser degree, lower ABI levels and poorer education in African Americans than in whites. Further study is needed to determine whether these findings affect racial treatment disparities and poorer outcomes previously reported in African Americans than in whites with PAD.     

Vitamin E reduces monocyte tissue factor expression in cirrhotic patients

Clotting activation may occur in liver cirrhosis, but the pathophysiological mechanism has not been fully elucidated. Because a previous study demonstrated that lipid peroxidation is increased in cirrhosis, we analyzed whether there is a relationship between lipid peroxidation and clotting activation. Thirty cirrhotic patients (19 men and 11 women; age, 34 to 79 years) and 30 controls matched for sex and age were investigated. In all subjects, monocyte expression of tissue factor (TF) antigen and activity; plasma levels of prothrombin fragment 1+2 (F1+2), a marker of thrombin generation; and urinary excretion of Isoprostane-F2alpha-III, a marker of lipid peroxidation, were measured. Furthermore, the above-reported variables were re-evaluated after 30 days of treatment with standard therapy (n = 5) or standard therapy plus 300 mg vitamin E twice daily (n = 9). In addition, we analyzed in vitro if vitamin E (50 micromol/L) influenced monocyte TF expression and F1+2 generation. Cirrhotic patients had higher values of Isoprostane-F2alpha-III (P <. 0001), F1+2 (P <.0001), and monocyte TF antigen (P <.0001) and activity (P <.03) than controls. Isoprostane-F2alpha-III was significantly correlated with F1+2 (Rho = 0.85; P <.0001) and TF antigen (Rho = 0.95; P <.0001) and activity (Rho = 0.94; P <.0001). After vitamin E treatment, Isoprostane-F2alpha-III (P =.008), F1+2 (P <.008), and monocyte TF antigen (P =.012) and activity (P =.008) significantly decreased; no changes of these variables were detected in patients not receiving vitamin E. In vitro, vitamin E significantly reduced the expression of monocyte TF antigen (-52%; P =.001) and activity (-55%; P =.003), as well as F1+2 generation (-51%; P =.025). This study shows that vitamin E reduces both lipid peroxidation and clotting activation and suggests that lipid peroxidation may be an important mediator of clotting activation in liver cirrhosis.     

Gait Alterations Associated with Walking Impairment in People with Peripheral Arterial Disease with and without Intermittent Claudication

OBJECTIVES: To describe gait alterations associated with impaired walking endurance in patients with and without lower-extremity peripheral arterial disease (PAD) and determine whether the Caltrac accelerometer provides a valid measure of physical activity in PAD. DESIGN: Cross-sectional. SETTING: Academic medical center. PARTICIPANTS: PAD (n = 40) and non-PAD patients (n = 22) from two Chicago hospitals. MEASUREMENTS: Participants underwent measurement of the ankle brachial index (ABI), leg length, and 6-minute walk. Steps per minute and step length were measured during the first and last 100 feet of the 6-minute walk. Participants wore a Caltrac accelerometer, sensitive to vertical acceleration, during the 6-minute walk and for 7 continuous days. RESULTS: Five PAD participants (13%) and one non-PAD participant (5%) ceased walking before the end of 6 minutes. Among the remaining participants, distance walked in 6 minutes was more highly related to walking velocity during the last 100 feet of the walk than walking velocity during the first 100 feet. ABI was associated significantly with cadence (20.77 steps/minute per unit ABI, P <.001) but not step length (10.12 centimeters/unit ABI, P =.08). ABI was associated significantly with 6-minute walk distance (493 feet/unit ABI, P =.018), but this association disappeared completely after adjustment for step length and cadence. We found no difference in accelerometer scores between PAD and non-PAD participants over a fixed distance of 800 feet (7.34 vs 7.17 activity units, P =.789). However, scores were significantly different after 7 days (730.8 vs 1,485.0 activity units, P =.003). CONCLUSION: Walking performance in PAD patients who completed 6 minutes of walking was largely determined by a decline in walking velocity rather than slower initial walking velocity. ABI was more closely associated with cadence than step length. Future studies should assess the effect of exercise programs and revascularization on cadence and step length in PAD.     

Knochendichte und 25-OH-Vitamin-D- Serumspiegel bei Patienten mit systemischem Lupus erythematodes

OBJECTIVE: To clarify the influence of vitamin D metabolism on bone mineral density (BMD) or bone metabolism in patients with systemic lupus erythematosus (SLE). METHODS: 57 consecutive patients in our department (mean age 33.9 years, 44 female, 13 male) were studied. BMD was measured with dual-X-ray absorptiometry at the lumbar spine and femoral neck. Biochemical investigation of bone metabolism included measurement of vitamin D metabolites, intact parathyroid hormone (PTH), serum osteocalcin und urinary pyridinoline-crosslink excretion. RESULTS: 25 patients had 25-OH cholecalciferol serum values below the normal range after adjustment for seasonal changes; 9 patients were severely vitamin D depleted with 25-OH vitamin D serum values below 5 ng/ml. Low 25-OH-vitamin D was significantly associated with high disease activity. Mean 1.25 (OH)2-vitamin D, PTH, osteocalcin and crosslink excretion were in the normal range. Thirty-six patients had normal BMD; 5 patients had osteoporosis according to WHO diagnosis criteria. No correlation of biochemical parameters of bone metabolism with BMD was found. CONCLUSION: Severe vitamin D depletion was common in this group of patients with SLE even after adjustment for seasonal variations, especially in patients with high disease activity. Therefore, D-hypovitaminosis should be included in the differential diagnosis in patients with SLE presenting with low bone mass.     

Alterations of bone mineral density and bone metabolism in patients with various grades of chronic pancreatitis

The aim of this study was to examine bone mineral density (BMD) and bone metabolism in patients with chronic pancreatitis to determine if increased severity of the disease would correlate with increased bone loss. Between October 1999 and September 2000, we investigated 42 patients with an average age of approximately 53 years suffering from chronic pancreatitis, as well as 20 healthy male controls with an average age of 49 years. Dual energy x-ray absorptiometry (DEXA) was performed on patients and controls, and serum levels of parathyroid hormone (PTH), osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (CICP), bone-specific alkaline phosphatase (BAP), 1,25(OH)(2) vitamin D(3) and 25(OH) vitamin D(3), as well as fecal elastase 1 were also determined. The severity of chronic pancreatitis in patients was determined via endoscopic retrograde cholangiopancreatography (ERCP) and assigned to 1 of 3 grades based on the Cambridge classification. BMD of patients with chronic pancreatitis was markedly decreased compared to controls (means in patients: DEXA lumbar vertebra anterior/posterior (LV ap) 96.8% +/- 4.2%, DEXA Ward's triangle (WARD) 92.2% +/- 5.2%; controls: DEXA LV ap 98.7% +/- 3.7%, DEXA WARD 97.1% +/- 3.1%; P <.05 and P <.0001) and correlated with the various Cambridge-grades (DEXA LV ap and DEXA WARD, P <.01). Fecal elastase 1 showed sensitivities of 14%, 87%, and 95% for the Cambridge-grades I, II, and III, respectively, and correlated with this classification of severity of chronic pancreatitis (P <.01). Furthermore, fecal elastase 1 of patients correlated the same way with both D(3)-vitamins (P <.01), as well as with parameters of BMD (P <.01). If fecal elastase 1 in patients was below 200 micro g/g, then the BMD and vitamin D(3) values were also significantly decreased compared to those with fecal elastase 1 above 200 micro g/g. In patients with Cambridge grades II and III 1,25(OH)(2)D(3) was markedly decreased (26.7 +/- 7.7 pg/mL and 27.6 +/- 9.0 pg/mL) compared to those with Cambridge grade I (38.0 +/- 10.5 pg/mL; between I and II, P =.027; between I and III, P =.033). 25(OH)D(3) was not significantly different within the various Cambridge groups (P =.07). Compared to controls, both D(3) vitamins, as well as fecal elastase 1, were extremely low (means in patients: fecal elastase 1, 140.7 +/- 75.7 micro g/g; 1,25(OH)(2)D(3), 29.9 +/- 9.5 pg/mL; 25(OH)D(3), 26.7 +/- 9.7 nmol/L; controls: fecal elastase 1, 694.9 +/- 138.6 micro g/g; 1,25(OH)(2)D(3), 67.5 +/- 4.3 pg/mL; 25(OH)D(3), 69.5 +/- 13.5 nmol/L). A significant correlation was observed between increased severity of chronic pancreatitis based on both endoscopic retrograde cholangiopancreatography and levels of fecal elastase 1, with decreased circulating levels of vitmain D(3) and decreased BMD. This supports a connection between the inflammatory destruction of the pancreas (Cambridge classification), exocrine pancreatic insufficiency (fecal elastase 1), altered levels of vitamin D metabolites, and loss of skeletal mass.     

Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily

OBJECTIVES: To study the effect of alfacalcidol (1alpha(OH)D3) on fall risk in community-dwelling elderly men and women. DESIGN: Randomized, double-blind, placebo-controlled intervention trial. SETTING: Basel, Switzerland. PARTICIPANTS: Three hundred seventy-eight community-dwelling elderly (191 women/187 men). INTERVENTION: Participants were randomly assigned to receive 1 microg of alfacalcidol or matched placebo daily for 36 weeks. MEASUREMENTS: Serum 25-hydoxyvitamin D3 (25(OH) D,1,25-dihydroxyvitamin D3 (D-hormone), and intact parathormone (iPTH) levels were measured using radioimmunoassay at baseline and every 12 weeks. Numbers of fallers and falls were assessed using a questionnaire during each study site visit. Dietary calcium intake was assessed at baseline using a food frequency questionnaire. RESULTS: At baseline, participants had, on average, normal vitamin D and D-hormone serum levels. Over 36 weeks, alfacalcidol treatment was associated with fewer fallers (odds ratio (OR)=0.69, 95% confidence interval (CI)=0.41-1.16) than placebo. In a post hoc subgroups analysis by medians of total calcium intake, this reduction reached significance in alfacalcidol-treated subjects with a total calcium intake of more than 512 mg/d (OR=0.45, 95% CI=0.21-0.97, P=.042) but not in those who consumed less than 512 mg/d (OR=1.00, 95% CI= 0.47-2.11, P=.998). Alfacalcidol treatment was also, independent of total calcium intake, associated with a significant 37.9% reduction in iPTH serum levels (P<.0001). No cases of clinically relevant hypercalcemia were observed. CONCLUSION: Provided a minimal calcium intake of more than 512 mg/d, alfacalcidol treatment significantly and safely reduces number of fallers in an elderly community dwelling population.     

Depressive symptoms and lower extremity functioning in men and women with peripheral arterial disease

OBJECTIVE: Factors associated with impaired functioning in patients with lower extremity peripheral arterial disease (PAD) are not fully understood. The purpose of this study was to determine the relationship between depressive symptoms and objective measures of lower extremity functioning in persons with PAD. DESIGN: Cross-sectional. PATIENTS/PARTICIPANTS: Four hundred twenty-three men and women with PAD identified from 3 Chicago area medical centers. MEASUREMENTS AND MAIN RESULTS: PAD was defined as ankle brachial index (ABI) <0.90. The Geriatric Depression Scale short form (GDS-S) (0-15 scale, 15 = worst) was completed by all participants. A clinically significant number of depressive symptoms was defined as a GDS-S score >or=6. Six-minute walk distance and usual-and fast-pace walking velocity were determined for all participants. A GDS-S score >or=6 was present in 21.7% of participants with PAD. Adjusting for age, increasing numbers of depressive symptoms were associated with an increasing prevalence of leg pain on exertion and rest (P =.004). Adjusting for age, sex, race, ABI, number of comorbidities, current smoking, and antidepressant medications, increasing numbers of depressive symptoms were associated with shorter 6-minute walk distance (P <.001), slower usual-pace walking velocity (P =.005), and slower fast-pace walking velocity (P =.005). These relationships were attenuated slightly after additional adjustment for presence versus absence of leg pain on exertion and rest and severity of exertional leg symptoms. CONCLUSIONS: Among men and women with PAD, the prevalence of a clinically significant number of depressive symptoms is high. Greater numbers of depressive symptoms are associated with greater impairment in lower extremity functioning. Further study is needed to determine whether identifying and treating depressive symptoms in PAD is associated with improved lower extremity functioning.     

Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from sub-Saharan Africa.

Among African immigrants in Melbourne, Victoria, Australia, we demonstrated lower geometric mean vitamin D levels in immigrants with latent tuberculosis infection than in those with no Mycobacterium tuberculosis infection (P=.007); such levels were also lower in immigrants with tuberculosis or past tuberculosis than in those with latent tuberculosis infection (P=.001). Higher vitamin D levels were associated with lower probability of any M. tuberculosis infection (P=.001) and lower probability of tuberculosis or past tuberculosis (compared with latent tuberculosis infection; P=.001).     

Vitamin D receptor gene polymorphisms and susceptibility to Mycobacterium malmoense pulmonary disease

Polymerase chain reaction using sequence-specific primers was utilized to ascertain the prevalence of 3 polymorphisms of the vitamin D receptor (VDR) gene (FokI F/f, ApaI A/a, and TaqI T/t) in 56 patients with Mycobacterium malmoense pulmonary disease. When compared with 101 controls, M. malmoense patients displayed an increased prevalence of Apa1 A (P=.03; Fisher's exact test), TaqI t (P=.04), and the At VDR haplotype (P=.04), and they displayed a decreased prevalence of FokI f (P=.04). Only 4 (7%) of 56 patients (vs. 29 [28%] of 101 controls) were both positive for FokI f and negative for At (P=.001). This indicates that polymorphisms in the VDR (or in closely linked genes) modulate the susceptibility to M. malmoense and that susceptibility involves multiple genetic and environmental factors.     

The prevalence of peripheral arterial disease in a racially diverse population

BACKGROUND: The purpose of this study was to determine the prevalence of peripheral arterial disease (PAD) in white, African American, and English- and Spanish-speaking Hispanic patients. METHODS: We screened patients older than 50 years for PAD at 4 primary care clinics located in the Houston Veterans Affairs Medical Center and the Harris County Hospital District. The disease was diagnosed by an ankle-brachial index of less than 0.9. Patients also completed questionnaires to ascertain symptoms of intermittent claudication, walking difficulty, medical history, and quality of life. RESULTS: We enrolled 403 patients (136 whites; 136 African Americans; and 131 Hispanics, 81 of whom were Spanish speaking). The prevalence of PAD was 13.2% among whites, 22.8% among African Americans, and 13.7% among Hispanics (P =.06). African Americans had a significantly higher prevalence of PAD than whites and Hispanics combined (P =.02). Among all patients who were diagnosed as having PAD on the basis of their ankle-brachial index, only 5 (7.5%) had symptoms of intermittent claudication. CONCLUSIONS: Peripheral arterial disease is a prevalent illness in the primary care setting. Its prevalence varies by race and is higher in African Americans than in whites and Hispanics. Relative to the prevalence of PAD, the prevalence of intermittent claudication is low. Since measurement of the ankle-brachial index is not part of the routine clinic visit, many patients with PAD are not diagnosed unless they develop symptoms of intermittent claudication. Because of this, it is likely that many patients remain undiagnosed. Efforts are needed to improve PAD detection in the primary care setting.     

Is serum phosphorus control related to parathyroid hormone control in dialysis patients with secondary hyperparathyroidism?

ABSTRACT: BACKGROUND: Elevated serum phosphorus (P) levels have been linked to increased morbidity and mortality in dialysis patients with secondary hyperparathyroidism (SHPT) but may be difficult to control if parathyroid hormone (PTH) is persistently elevated. We conducted a post hoc analysis of data from an earlier interventional study (OPTIMA) to explore the relationship between PTH control and serum P. METHODS: The OPTIMA study randomized dialysis patients with intact PTH (iPTH) 300-799 pg/mL to receive conventional care alone (vitamin D and/or phosphate binders [PB]; n = 184) or a cinacalcet-based regimen (n = 368). For patients randomized to conventional care, investigators were allowed flexibility in using a non-cinacalcet regimen (with no specific criteria for vitamin D analogue dosage) to attain KDOQITM targets for iPTH, P, Ca and Ca x P. For those assigned to the cinacalcet-based regimen, dosages of cinacalcet, vitamin D sterols, and PB were optimized over the first 16 weeks of the study, using a predefined treatment algorithm. The present analysis examined achievement of serum P targets ([less than or equal to]4.5 and [less than or equal to]5.5 mg/dL) in relation to achievement of iPTH [less than or equal to] 300 pg/mL during the efficacy assessment phase (EAP; weeks 17-23). RESULTS: Patients who achieved iPTH [less than or equal to] 300 pg/mL (or a reduction of [greater than or equal to]30% from baseline)were more likely to achieve serum P targets than those who did not, regardless of treatment group. Of those who did achieve iPTH [less than or equal to] 300 pg/mL, 43% achieved P [less than or equal to]4.5 mg/dL and 70% achieved P [less than or equal to]5.5 mg/dL, versus 21% and 46% of those who did not achieve iPTH [less than or equal to] 300 pg/mL. Doses of PB tended to be higher in patients not achieving serum P targets. Patients receiving cinacalcet were more likely to achieve iPTH [less than or equal to]300 pg/mL than those receiving conventional care (73% vs 23% of patients). Logistic regression analysis identified lower baseline P, no PB use at baseline and cinacalcet treatment to be predictors of achieving P [less than or equal to]4.5 mg/dL during EAP in patients above this threshold at baseline. CONCLUSIONS: This post hoc analysis found that control of serum P in dialysis patients was better when serum PTH levels were lowered effectively, regardless of treatment received. Clinicaltrials.gov identifier NCT00110890.     

Hypercalcemia in rheumatoid arthritis: relationship with disease activity and bone metabolism

To investigate the relationship between ionized calcium and disease activity, parameters of bone metabolism and bone mineral density (BMD) at the lumbar spine (BMD-LS) and the femoral neck (BMD-FN) measured by dual X-ray absorptiometry in rheumatoid arthritis (RA). In 146 patients with RA, the following parameters were investigated: serum levels of ionized calcium, total calcium, vitamin D metabolites 25-hydroxyvitamin D3 (25D3) and 1,25-dihydroxyvitamin D3 (1,25D3), intact parathyroid hormone (iPTH), interleukin-6, osteocalcin, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP); renal excretion of pyridinolin (PYD)- and desoxypyridinolin (DPD)-crosslinks. A total of 30.1% of the patients were hypercalcemic (ionized calcium >1.30 mmol/l). In comparison with normocalcemic patients, those with hypercalcemia had significantly higher ESR (P<0.01) and CRP values (P<0.05) and significantly lower serum levels of both iPTH (P<0.01) and 1,25D3 (P<0.05) and a significantly lower BMD-LS (P<0.05). The results indicate that a substantial part of RA patients is hypercalcemic. Hypercalcemia is associated with high disease activity and may contribute to suppression of PTH secretion and vitamin D hormone synthesis. High levels of ionized calcium may be a reflection of disease-activity-related systemic bone loss, and could be a predictor of BMD at the lumbar spine in RA.