2nd Quartiles Research Articles

Longitudinal Study on White Blood Cell Count and the Incidence of Metabolic Syndrome

Many studies have revealed that white blood cell count (WBC) is related to insulin resistance which is a central mechanism of metabolic syndrome (MetS). However, few cohort studies have examined the role of WBC in the development of MetS. We hypothesized that WBC is associated with the future development of MetS, and investigated the longitudinal incidence of MetS in healthy workers. WBC was measured in 5,073 workers (mean age 42.5 years) without MetS at baseline. The incidence of MetS was monitored over 7 years of follow-up, in relation to quartiles of WBC. During the follow-up, 925 participants were diagnosed as MetS. Incidence of MetS was increased in participants with higher WBC: the rates of incidence of MetS were 22.6, 32.9, 42.9, and 57.5 per 1,000 person-years of follow-up in the 1st, 2nd, 3rd, and 4th quartiles of WBC, respectively. After adjustments for confounding factors, the adjusted hazards ratio (95% confidence interval) for MetS was 1.00 (reference), 1.22 (0.98 to 1.51), 1.52 (1.24 to 1.87), and 1.66 (1.35 to 2.04) through the quartiles of WBC, respectively, (p <0.001). This relationship was consistent among current smokers and never smokers, and among male and female genders, respectively. WBC is useful in predicting the future development of MetS which leads to atherosclerotic diseases.

Total, direct, and indirect serum bilirubin concentrations and metabolic syndrome among the Korean population

Total bilirubin, not direct or indirect bilirubin, has been reported to associate inversely with metabolic syndrome. Therefore, we aimed to evaluate the association between bilirubin subtypes and metabolic syndrome among the Korean population. This study included 5,231 Koreans (3,008 men, 2,223 women) aged 30-87years, who visited the Health promotion centers in Seoul from April, 2006 to June, 2007. The associations of direct, indirect, and total bilirubin classified in quartiles with metabolic syndrome were measured by logistic regression analyses in men and women. Odds ratios (95% confidence intervals) of the lowest, 2nd and 3rd quartiles of direct serum bilirubin compared with the highest quartile (reference) were 2.3 (1.6-3.2), 1.8 (1.3-2.4), and 1.8 (1.4-2.4) among men, and 5.5 (2.6-11.5), 3.1 (1.5-6.7), and 1.9 (0.9-4.3) among women, respectively. In a multivariable adjusted model, however, the significance of inverse associations with total and indirect bilirubin became attenuated. The relation was consistent particularly with direct bilirubin in subgroups of metabolic syndrome components such as central obesity, hypertriglyceridemia, hyperglycemia, and low HDL-cholesterol in both men and women. Of the three subtypes of serum bilirubin, the inverse association of metabolic syndrome was significantly apparent and consistent with direct bilirubin.

Bone mineral density and risk of postmenopausal breast cancer

To determine if higher bone mineral density (BMD) is a risk factor for breast cancer in women age 50 years and older. 37,860 women ≥ 50-year old with no previous breast cancer diagnosis had baseline BMD assessment between January 1999 and December 2007. Cox proportional hazards models were created for time to a new breast cancer as a function of lumbar spine or femoral neck BMD quartile (1st = lowest as reference) with adjustment for relevant covariates. A secondary analysis was performed to look for an association with estrogen receptor-positive (ER-positive) breast cancers. 794 invasive and in situ breast cancers (484 ER-positive) occurred with a median follow up of 5.4 years. Increased breast cancer risk was seen for the 3rd and 4th quartiles of lumbar spine BMD with hazard ratios (HRs) of 1.26 (95% CI, 1.01-1.58) and 1.45 (95% CI, 1.16-1.81), respectively and for the 3rd quartile of femoral neck BMD with a HR of 1.33 (95% CI, 1.07-1.64). A test for linear trend showed that lumbar spine BMD (P < 0.001) and femoral neck BMD (P = 0.04) were associated with increased risk. Higher lumbar spine BMD was also associated with increased risk of ER-positive breast cancer with HR of 1.45 (95% CI, 1.08-1.94), and 1.68 (95% CI, 1.24-2.27) for women in the 2nd and 4th quartiles, respectively. A test for linear trend showed lumbar spine BMD was associated with increasing risk of ER-positive breast cancer (P = 0.003). Increased ER-positive breast cancer risk was seen for the 3rd quartile of femoral neck BMD with a HR of 1.43 (95% CI, 1.08-1.89). Higher lumbar spine and femoral neck BMD are associated with higher risk of breast cancer in women ≥50-year old. Lumbar spine and femoral neck BMD are associated with increased risk of ER-positive breast cancer.

Serum levels of vitamin D, PTH and calcium and breast cancer risk—a prospective nested case–control study

Previous studies indicate that calcium and its regulating hormones, i.e., parathyroid hormone (PTH) and vitamin D, might affect breast cancer risk. Evidence also suggests that this relationship could be influenced by menopausal status and BMI. We examined breast cancer risk related to prediagnostic serum levels of vitamin D (25OHD(2) and 25OHD(3)), PTH and calcium using a nested case-control design within the Malmö Diet and Cancer Study. There were 764 incident breast cancer cases, and 764 controls were selected by incidence density matching, using age as the underlying time scale, matching on calendar time at inclusion, menopausal status and age at inclusion. Using logistic regression analysis, odds ratios (OR) with 95% confidence intervals were calculated for breast cancer risk in different quartiles of the analyzed factors. All analyses were adjusted for risk factors for breast cancer, and for levels of albumin, creatinine and phosphate. Analyses were repeated stratified for BMI and menopausal status, and for low vs. high levels of 25OHD(3), PTH and calcium. There was a weak, nonsignificant inverse association between breast cancer risk and 25OHD(3), and the OR for the 2nd, 3rd and 4th quartiles, as compared to the first, were 0.84 (0.60-1.15), 0.84 (0.60-1.17) and 0.93 (0.66-1.33). Serum calcium was positively associated with breast cancer in premenopausal women (OR for the 4th quartile = 3.10:1.33-7.22 and p for quartile trend = 0.04), and in women with BMI > 25 (OR for the 4th quartile = 1.94:1.12-3.37 and p for trend < 0.01). There was no association between baseline serum PTH and breast cancer risk.

Radiation exposure during computed tomography-guided cryoablation of renal masses.

e15116 Background: Despite heightened awareness of risks from ionizing radiation, the use of image-guided therapy is rising. Our goal was to calculate the radiation effective dose (ED) received during computed tomography (CT)-guided percutaneous cryoablation (PC) of renal masses. Methods: A retrospective chart review from January 2008 to June 2009 found 21 patients had undergone CT-guided PC. Using radiation dose estimates from the procedures based on a standard anthropomorphic phantom, mean radiation ED was estimated. Fluoroscopy time and total ED were used to compute the learning curve which was assessed with correlation testing. Results: We performed PC on 24 masses ranging from 0.9-8.0cm. Mean patient age, body mass index, and lesion size were 65.8 years, 28.3, and 2.9 cm, respectively. For each mass ablated, mean fluoroscopy time was 46.4 seconds (range 11.4-143.4 sec), mean fluoroscopy ED was 8.2 mSv (range 1.9-28.0 mSv), and mean total ED was 21.6 mSv (range 10.1-37.5 mSv). We estimated the learning curve by dividing the 24 masses into quartiles and calculated the mean mass size, fluoroscopy time, and total ED per quartile. There was a 59.3% decrease in fluoroscopy time and a 39.4% decrease in total ED between the 1st and 4th quartile despite a 17.7% increase in mass size. Fluoroscopy time was moderately correlated with case number (R2=0.32). When plotting fluoroscopy time utilized per individual mass versus case number a decline was seen (R2=0.35). Fluoroscopy time alone was minimally correlated with mass size (R2=0.19) and not at all with BMI (R2=0.05). Conclusions: Fluoroscopy time declined as operator experience increased, subjecting patients to less radiation exposure. Mean total radiation ED was 21.6 mSv for all cases. For comparison, three-phase renal CT ED on our scanner was 23.7 mSv. While the greatest decline in fluoroscopy time (51.0%) occurred between the 1st and 2nd quartile, there was still an 11.0% time decrease between the 3rd and 4th quartile suggesting continued improvement in the learning curve. No significant financial relationships to disclose.

Abstract 2824: A prospective evaluation of dietary indole-3-carbinol in relation to risk of lung cancer in the Singapore Chinese Health Study

Abstract Background: Indole-3-carbinol (I3C) is a naturally occurring hydrolysis product of glucobrassicin, a glucosinolate found in cruciferous vegetables. I3C has been shown to inhibit carcinogen-induced occurrence of cancer in multiple organs including lung in experimental animals. High consumption of dietary glucobrassicins was inversely related to urinary levels of NNAL, a metabolite of the tobacco-specific lung carcinogen NNK. Data on the dietary intake of I3C or its precursors and lung cancer risk in humans are lacking. Methods: We prospectively examined the association between dietary intake of glucobrassicins and risk of lung cancer in the Singapore Chinese Health Study, a cohort of 63,257 middle-aged and older Chinese men and women enrolled between 1993 and 1998. Dietary intake of glucobrassicins was derived from a validated, semi-quantitative food-frequency questionnaire administered to subjects in person at enrollment and the quantified amount of glucobrassicin in specific cruciferous vegetables purchased from Singapore markets. We had complete follow-up for incidence of cancer and death among cohort participants through computer record linkage analysis to the nation-wide Singapore cancer and death registries. As of December 31, 2007, 1,104 incident cases of lung cancer were identified within the cohort. Cox proportional hazards regression was used to evaluate the association between dietary intake of glucobrassicins and lung cancer risk. The regression model included age, body mass index (kg/m2), year of interview, gender, dialect group, level of education, smoking status, number of cigarettes/day and years of cigarette smoking, dietary intake of beta-cryptoxanthin, and total calorie intake. Results: After adjustment for number of cigarettes/day, number of years of smoking and other potential confounders, current smokers with high intake of glucobrassicins had a borderline statistically significant reduced risk of lung cancer (Ptrend=0.08). Compared to the lowest quartile, hazard ratios (HR) [95% confidence intervals (CI)] for the 2nd, 3rd, and 4th quartile of glucobrassicins were 0.94 (0.77-1.15), 0.95 (0.76-1.18) and 0.77 (0.59-0.99), respectively. This inverse association was more evident after excluding the first 5-years of follow-up; the corresponding HR (95% CI) were 0.89 (0.70-1.14), 0.93 (0.72-1.21) and 0.61 (0.44-0.85) (Ptrend=0.01). The present study did not show an inverse association between dietary isothiocyanate (ITC) intake and lung cancer in current smokers. Neither I3C precursors nor ITC was related to risk of lung cancer in never or former smokers. Conclusion: High intake of dietary glucobrassicins was associated with reduced incidence of lung cancer in smokers. The findings of this study suggest that I3C precursors rather than ITC present in cruciferous vegetables may exert a protective role in the development of lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2824.

Metabolic syndrome risk is associated with lower cardiovascular fitness and daily activity levels among young adults

Research related to metabolic syndrome (MbS) and chronic disease risk in young adults (18–24) is lacking. The Young Adult Health Risk Screening Initiative is an ongoing cross‐sectional investigation of chronic disease risk among students at the University of New Hampshire. We have previously reported that MbS criteria are higher in young adults with lower self‐reported levels of physical activity. To validate this finding, we examined MbS in relation to cardiovascular fitness via 1‐mile Rockport Walk Test and daily activity via 7‐day pedometer step log (n=256, 69% women). MbS criteria include abdominal obesity (waist ≥ 40 in), hypertrigylceridemia (≥ 150 mg/dl), low HDL‐C (&lt; 40 mg/dl), hypertension (≥ 130/85 mm Hg), and elevated glucose (≥ 100 mg/dl). Mean number of MbS criteria was 1.0±0.06; mean VO2max was 48.8±.4 ml/kg·min; &amp; mean steps per day was 9215±184. Young adults in the top quartile for cardiovascular fitness (VO2max) had lower number of MbS criteria as compared to those in lowest quartile (0.7±.1 vs. 1.3±.1, p&lt;.05). Young adults in the lowest quartile for daily activity (steps per day) had greater number of MbS criteria as compared to those in the 2nd and 3rd quartiles (1.3±.1 vs. 0.9±.1, p=.05; 1.3±.1 vs. 0.9±.1, p&lt;.05). These findings validate our previous work and demonstrate that fitness level and daily activity are negatively associated with MbS criteria in young, college adults.Grant Funding Source: NH Agricultural Experiment Station

Long-term changes in serum cholesterol level does not influence the progression of coronary calcification

Background A number of reports controversially describe the influence of cholesterol level and lipid-lowering treatment (LLT) on the progression of coronary calcium (CC). We tested the hypothesis that long-term changes in serum cholesterol (CL) would affect the progression of CC. Methods The study population comprised 510 patients with stable angina pectoris, mean age of 63 ± 9 years. At baseline 372 patients received statin and/or fibrate (LLT group) while 138 patients did not (No-LLT at baseline group). Spiral CT every 24 months was used to track the progression of CC over a median 5.6 year follow-up. Results CL decreased during follow-up in both groups, but more pronouncedly in patients with LLT. The changes in total calcium score (TCS) were similar in both groups ( p = 0.3). Changes in CL during follow-up were not associated with CC: TCS increased by 501 ± 63 from baseline in the 1st (upper) quartile, and by 350 ± 44, 403 ± 41 and 480 ± 56 in the 2nd, 3rd, and 4th quartiles of CL longitudinal changes ( p = 0.2), respectively. Baseline TCS and its changes were not correlated with baseline CL and its changes. New calcified lesions were diagnosed in 132 (28.2%) out of the 467 patients available for this analysis, without significant difference between groups ( p = 0.4). Multivariate analysis demonstrated that only baseline TCS ( p < 0.001), body mass index ( p = 0.007) and age ( p = 0.006) were independent predictors for the TCS changes. Conclusions Longitudinal CL changes do not seem to have a measurable effect on the rate of progression of CC.

Plasma Levels of Acid-Labile Subunit, Free Insulin-Like Growth Factor-I, and Prostate Cancer Risk: A Prospective Study

The acid-labile subunit (ALS) acts in the insulin-like growth (IGF) system by binding circulating IGF-I in a ternary complex with binding protein (IGFBP)-3 to prevent IGF-I from crossing the endothelial barrier. Given the role of the IGF system in prostate cancer, ALS may influence carcinogenesis by modulating IGF-I levels or bioavailability. We undertook a prospective study nested in the Physicians' Health Study to examine ALS, free IGF-I, and prostate cancer. We assayed circulating levels of ALS and IGF components among 545 incident cases and 545 matched controls. We calculated relative risks (RR) and 95% confidence intervals (95% CI) adjusted for life-style factors, total IGF-I, and IGFBP3. ALS was positively correlated with total IGF-I (r = 0.58), IGFBP3 (r = 0.68), and free IGF-I (r = 0.36). Comparing highest versus lowest quartiles, we found no association between free IGF-I and prostate cancer risk (RR, 0.9; 95% CI, 0.6-1.3). In contrast, ALS was positively associated with risk among men in the 2nd (RR, 1.5; 94% CI, 1.0-2.3), 3rd (RR, 1.6; 94% CI, 1.1-2.5), and 4th quartiles (RR, 1.4; 94% CI, 0.9-2.1) compared with lowest quartile. The association was stronger for advanced stage tumors (RR, 2.0; 94% CI, 0.8-4.6). There was a suggestion of an interaction between ALS and total IGF-I, whereby high circulating IGF-I was associated with an increased risk of advanced prostate cancer among men with low but not higher ALS levels. Plasma ALS is positively associated with prostate cancer risk, and may interact biologically with IGF-I to affect carcinogenesis. These data provide further support for the role of the IGF axis in prostate cancer.

Impact of body mass index on clinical outcome in patients with acute coronary syndromes treated with percutaneous coronary intervention

Studies that have tested the relationship between body weight as assessed by body mass index (BMI) and clinical outcome after percutaneous coronary intervention (PCI) have given contradictory results. The aim of the study was to investigate the impact of BMI on clinical outcome and assess the impact of adjustment for other cardiovascular risk factors on the relationship between obesity and clinical outcome in patients with acute coronary syndromes (ACS) following PCI. This study included 9146 patients with ACS who underwent coronary angiography and PCI: 2610 patients with ST-segment elevation acute myocardial infarction, 2792 patients with non-ST-segment elevation acute myocardial infarction, and 3744 patients with unstable angina. The primary outcome of this analysis was 1-year mortality. Quartiles of BMI were: 12.8 to <24.3 (1st quartile), 24.3 to <26.4 (2nd quartile), 26.4 to <29.1 (3rd quartile), and >29.1 to 50.7 (4th quartile). Within the first year following PCI, there were 756 deaths: 228 deaths in the 1st BMI quartile, 209 deaths in the 2nd BMI quartile, 161 deaths in the 3rd BMI quartile and 158 deaths in the 4th BMI quartile (Kaplan-Meier estimates of mortality 10.3%, 9.1%, 7.2%, and 7.0%, respectively; odds ratio [OR] = 1.51, 95% confidence interval [CI] 1.22-1.86, P < 0.001 for 1st vs 4th BMI quartile). After adjustment in the Cox proportional hazards model, the association between BMI and 1-year mortality was attenuated to the level of statistical insignificance (hazards ratio [HR] = 1.25, 95% CI 0.94-1.64; P = 0.127 for 1st vs 4th BMI quartile). In conclusion, in patients with ACS undergoing PCI, obesity as assessed with BMI was not an independent correlate of 1-year mortality.

Low calcium:phosphorus ratio in habitual diets affects serum parathyroid hormone concentration and calcium metabolism in healthy women with adequate calcium intake

Excessive dietary P intake alone can be deleterious to bone through increased parathyroid hormone (PTH) secretion, but adverse effects on bone increase when dietary Ca intake is low. In many countries, P intake is abundant, whereas Ca intake fails to meet recommendations; an optimal dietary Ca:P ratio is therefore difficult to achieve. Our objective was to investigate how habitual dietary Ca:P ratio affects serum PTH (S-PTH) concentration and other Ca metabolism markers in a population with generally adequate Ca intake. In this cross-sectional analysis of 147 healthy women aged 31-43 years, fasting blood samples and three separate 24-h urinary samples were collected. Participants kept a 4-d food record and were divided into quartiles according to their dietary Ca:P ratios. The 1st quartile with Ca:P molar ratio < or = 0.50 differed significantly from the 2nd (Ca:P molar ratio 0.51-0.57), 3rd (Ca:P molar ratio 0.58-0.64) and 4th (Ca:P molar ratio > or = 0.65) quartiles by interfering with Ca metabolism. In the 1st quartile, mean S-PTH concentration (P = 0.021) and mean urinary Ca (U-Ca) excretion were higher (P = 0.051) than in all other quartiles. These findings suggest that in habitual diets low Ca:P ratios may interfere with homoeostasis of Ca metabolism and increase bone resorption, as indicated by higher S-PTH and U-Ca levels. Because low habitual dietary Ca:P ratios are common in Western diets, more attention should be focused on decreasing excessively high dietary P intake and increasing Ca intake to the recommended level.

Carotid Intima-Media Thickness, Systemic Inflammation, and Incidence of Heart Failure Hospitalizations

This study explored the relationships between carotid intima-media thickness (IMT), plasma levels of C-reactive protein (CRP), and incidence of heart failure hospitalizations. Men and women from the general population (n=4691), without history of myocardial infarction or stroke, were examined. Incidence of hospitalizations attributable to heart failure was studied over a mean follow-up of 13 years. A total of 75 subjects were hospitalized with a primary diagnosis of heart failure. Adjusted for risk factors, the hazards ratios (95% CI) were 1.00, 0.98 (0.36 to 2.7), 1.9 (0.80 to 4.6), and 2.7 (1.1 to 6.2), respectively, for the 1st, 2nd, 3rd, and 4th quartiles of IMT (P for trend=0.003). The HR associated with CRP levels >or=3 mg/L (versus <1 mg/L) was 2.0 (95% CI: 1.06 to 3.9) after adjustments for risk factors. There was a significant interaction between IMT and CRP on heart failure incidence (P=0.028). Subjects with CRP >or=3 mg/L and IMT in the 4th quartile had an adjusted HR of 3.7 (1.9 to 7.1) compared to those with CRP <3 mg/L and IMT in quartile 1 to 3. High IMT and high CRP are both independent risk factors for incidence of heart failure requiring hospitalization. The joint exposure to both risk factors substantially increases the risk.

Dietary Intake of Vegetables and Fruits and the Modification Effects of GSTM1 and NAT2 Genotypes on Bladder Cancer Risk

We analyzed the association between intakes of vegetables and fruits as defined by the U.S. Department of Agriculture pyramid food groups and bladder cancer risk using data collected in a large case-control study. The study included 884 histologically confirmed bladder cancer cases and 878 healthy controls matched to cases by age (+/-5 years), gender, and ethnicity. Significant inverse associations were observed for intakes of total vegetables, cruciferous vegetables, orange vegetables, dark green vegetables, and bladder cancer risk. Compared with those in the lowest quartile of total vegetable intake, the odds ratios for the 2nd, 3rd, and 4th quartiles of total vegetable intake were 0.84 [95% confidence interval (95% CI), 0.64-1.10], 0.71 (95% CI, 0.54-0.95), and 0.67 (95% CI, 0.50-0.90), respectively (P for trend = 0.004). Compared with those in the lowest quartile, those in the highest quartile of cruciferous vegetable intake had an odds ratio of 0.69 (95% CI, 0.52-0.92; P for trend = 0.001) and those in the highest quartile of orange vegetable intake had an odds ratio of 0.68 (95% CI, 0.52-0.91; P for trend = 0.006). Furthermore, the protective effect of cruciferous vegetables was more evident in subjects carrying GSTM1-null (odds ratio, 0.43; 95% CI, 0.25-0.73 for the 4th quartile of intake) and NAT2-slow genotypes (odds ratio, 0.56; 95% CI, 0.33-0.97 for the 4th quartile of intake). No association was observed for intakes of total fruits or citrus fruits. Our data strongly support that high vegetable consumption, especially cruciferous vegetable intake, may protect against bladder cancer and that genetic variants of GSTM1 and NAT2 may modify the association.

TU‐C‐304A‐08: A Method to Adjust CTDI to Better Represent the Dose for Pediatric Patients

Purpose: CT manufacturers are required to report dose using standardized CTDI phantoms. However, CTDI can be confusing when applied to pediatric patients due to variations in patient size. We propose a simple method to scale standard CTDI to better represent a pediatric patient's dose by providing universal conversion tables that are indexed by patient size ranges. Method and Materials: The Medical Imaging and Technology Alliance (MITA) and Image Gently Pediatric CT Physics Work Group have obtained CTDI ratios between the 32 cm, 16 cm and 10 cm phantoms for current 16 and 64 slice scanners. X‐ray attenuation was measured for the CTDI phantoms and retrospectively determined from pediatric and adult pre‐scan projection images. Regression relationships between patient dimensions, attenuation and dose ratios were used to create tables of CTDI scale factors as a function of patient dimensions. Results: The range of attenuation ratios of the 2nd and 3rd quartiles for pediatric heads compared to the standard CTDI phantoms was 0.85 to 0.95 (16 cm) and 0.46 to 0.51 (32 cm). The range for pediatric bodies was 1.03 to 1.35 (16 cm) and 0.85 to 0.95 (32 cm). Individual measurement errors relative to the mean CTDI ratio due to manufacturer, scanner generation and kVp or bowtie filter selections were minimal. Preliminary results show errors increased from 0 % to 14 % with increasing difference between the attenuation of the pediatric patient and CTDI phantom. Conclusion: Universal dose conversion tables can be provided based on dimensions or can be automatically calculated from a patient's attenuation determined from a pre‐scan projection image with reasonable accuracy to scale CTDI or its future replacement to better represent dose for pediatric patients.

Leukocyte Count and Incidence of Hospitalizations Due to Heart Failure

Leukocyte concentration in blood is a classical marker of systemic inflammation. Whether high leukocyte counts are associated with incidence of heart failure (HF) is unknown. This population-based study explored whether the leukocyte concentrations were associated with incidence of hospitalizations due to HF. Leukocyte counts were measured in 16 940 men from the general population (mean age 44 years) without history of myocardial infarction or stroke. Incidence of hospitalizations due to HF (primary diagnosis) was monitored over 23 years of follow-up, in relation to quartiles of leukocytes. Subjects with myocardial infarction during follow-up were censored in the main analysis. During the follow-up, 436 men were hospitalized due to HF. Incidence of HF hospitalizations was increased in men with high leukocyte counts. After adjustments for confounding factors, the adjusted hazards ratio (HR, 95% CI) for HF hospitalization was 1.00 (reference), 1.26 (0.93 to 1.7), 1.24 (0.91 to 1.7), and 1.73 (1.3 to 2.3), respectively, for men with leukocytes in the 1st, 2nd, 3rd, and 4th (highest) quartiles (trend, P<0.001). This relationship was consistent in smokers and nonsmokers and in men with and without hypertension, respectively. High leukocyte counts in middle-aged men were associated with increased long-term incidence of HF hospitalizations.

Uric Acid is Positively Associated with Metabolic Syndrome but Negatively Associated with Diabetes in Japanese Men

The relationships between uric acid and metabolic syndrome (MetS) and diabetes, as well as the gender differences in these relationships are controversial. Medical check-up data from 2,449 Japanese men and 1,448 Japanese women were examined. The prevalence of MetS and diabetes was calculated by the quartiles of serum levels of uric acid. Correlation coefficients between uric acid and MetS-related risk factors were calculated and compared between men and women. The prevalence of MetS in the 3rd quartile (Q3) of uric acid was significantly higher than that in the 1st (lowest) quartile (Q1) and the prevalence of MetS in the 4th quartile (Q4) was significantly higher than that in Q1, the 2nd quartile (Q2), and Q3 in men. The prevalence of MetS in Q4 was significantly higher than that in Q1, Q2, and Q3 in women. The prevalence of diabetes in Q3 was significantly lower than that in Q1 and the prevalence of diabetes in Q4 was significantly lower than that in Q1 and Q2 in men. The prevalence of diabetes was not significantly different among the quartiles of uric acid in women. The age-adjusted correlation coefficient between uric acid and fasting glucose was not significant in men. Uric acid is positively associated with metabolic syndrome but negatively associated with diabetes in Japanese men.

Correlation of CD 33 Expression Level with Disease Characteristics and Response to Gemtuzumab Ozogamycin-Containing Chemotherapy in Childhood AML

Gemtuzumab Ozogamycin (GO, Mylotarg), a humanized CD33-Chalechiamycin conjugate has been incorporated as an integral part of therapy of relapsed and de novo AML. Early data generated in relapsed AML using single agent GO demonstrated higher degree of response to GO in patients with high CD33 expression that correlated with lower multi drug resistance (MDR). There is little data on the efficacy of GO in those with low CD33 expression in de novo setting using GO in combination with conventional chemotherapy. Current therapies that utilize GO include patients with low or no CD33 expression. Children's Oncology Group (COG) AML pilot protocol COG AAML03P1 studied the feasibility of combining GO with MRC based chemotherapy in selected courses in patients with de novo AML regardless of CD33 expression level. We hypothesized that patients with low or no CD33 expression may have a different outcome (more inferior) from those with higher CD33 expression in this GO-based therapy. We prospectively evaluated the CD33 expression level of diagnostic blast cells and correlated the CD33 expression level with disease characteristics and clinical outcome. Of the 341 patients treated in COG AAML03P1, 240 diagnostic specimens were available for evaluation. CD33 expression level of the diagnostic leukemic blasts was determined by measuring the CD33 Mean Fluorescence Intensity (MFI). MFI of the blast population varied over 2 log fold from a baseline of 6.33 to 1551 with a median of 117.7. Study population was divided into quartiles based on CD33 expression: 1st Q: (MFI 6.33 – 57.054), 2nd Q: (MFI 57.1 – 117.7), 3rd Q: (MFI 117.7 – 209.3) and 4th Q (MFI 209.3 and higher). Remission induction rate (CR) at the end of induction and the clinical outcome was compared between the four groups. Patients with the lowest CD33 expression had a similar CR rate as those with higher CD33 expression (86% vs. 85%, = 0.980). In patients with the lowest CD33 expression (1st quartile), relapse risk and disease-free survival was not different than those in 2nd quartile (p=0.5 and 0.1, respectively), suggesting that paucity of CD33 expression does not portend poor outcome. Surprisingly, patients with the highest CD33 expression (4th quartile) had a worse outcome with disease-free survival of 45%, compared to that of 62% in those with lower CD33 expression (hazard ratio=1.69; p=0.02). Disease characteristics and molecular and cytogenetic make up of the patients were evaluated within the four groups. CD33 expression level was not associated with age, gender, diagnostic WBC or blast percentage. However, there was an inverse association between CD33 expression and the prevalence of CBF AML where in those with the lowest CD33 expression (1st quartile), 45% had CBF AML (inv(16) or t(8;21)). There was a step-wise decrease in the prevalence of CBF AML of 28%, 20% and 13% in the 2nd, 3rd and 4th quartiles, respectively. There was also an increased prevalence of FLT3/ITD with increasing CD33 expression with a prevalence of 3%, 12%, 15% and 18% in quartiles 1–4, respectively. Conversely, median CD33 MFI in favorable risk patients (CBF AML, NPMc or CEBPA) was 75 compared to those with FLT3/ITD or high risk cytogenetics who had a CD33 MFI of 170. This study demonstrates significant heterogeneity of CD33 expression and inverse association of CD33 expression level with clinical outcome, where those with low CD33 expression have a favorable outcome. This association with clinical outcome is directly linked to the underlying molecular/cytogenetic make up of the disease.

Is Ischemic Stroke Risk Related to Folate Status or Other Nutrients Correlated With Folate Intake?

Folate status was inversely associated with plasma homocysteine concentration, a potential risk factor of cardiovascular disease. However, it is uncertain whether folate is causally associated with risk of ischemic stroke (IS). We aimed to examine the association between IS incidence and folate intake, biochemical folate status, and folate associated nutrients. Information on baseline characteristics and food frequency questionnaire was collected in 1990 to 1993 and included for analyses data from 1772 adults over 40 years, who were free of stroke and cancer at baseline from the CardioVascular Disease risk FACtor Two-township Study. Multivariate Cox proportional hazard model was used to relate baseline nutrient status with IS event. Over an average of 10.6 years of follow-up, 132 incident IS events were documented. Low folate intake (1st and 2nd quartiles) was significantly and independently associated with increased IS risk (HR=1.61; 95% CI: 1.04 to 2.48 and HR=1.82; 95% CI: 1.20 to 2.76) compared with those in the 3rd and 4th quartile combined, whereas no association was observed for plasma folate concentration. On the other hand, several nutrients correlated with dietary folate: vitamin B2, potassium, iron, vitamin A of plant origin, calcium were also associated with IS risk in an inverse linear manner with HR ranging from 1.5 to 1.9 for the first quartile. The protective association of dietary folate on IS risk may be in part through that of other correlated nutrients or other dietary components.

Relationship of age-related concentrations of serum FSH and LH with bone mineral density, prevalence of osteoporosis in native Chinese women

Background Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) may play an important role in bone mass regulation in postmenopausal women. Methods A cross-sectional study of 699 healthy Chinese women, aged 20 to 82 y, was conducted. Serum FSH and LH and BMD were measured at the posteroanterior (PA) spine, lateral spine, total hip, and distal forearm. Results The geometric mean values (± SD) of serum FSH and LH in premenopausal women were 3.94 ± 2.08 and 7.51 ± 2.58 IU/l, respectively, and in postmenopausal women were 28.8 ± 1.88 and 25.6 ± 1.95 IU/l, respectively. The correlation of FSH to BMD at different skeletal regions ( r = − 0.597 – − 0.492, P = 0.000) was higher than that of LH to BMD ( r = − 0.452 – − 0.332, P = 0.000). The prevalences of osteoporosis for the quartiles of FSH at various skeletal sites were 0.57%, 0.43%, 27.1%, and 30.9%, respectively; and of LH were 2.14%, 4.43%, 19.5%, and 26.0%, respectively. The prevalence of osteoporosis in 3rd and 4th quartile was more significantly increased than the 1st and 2nd quartile. Conclusions These data suggest that FSH and LH levels in circulation are associated with BMD changes and osteoporosis occurrence in Chinese women.

Is it worth testing for AMH in young oocyte donors?

Is it worth testing for AMH in young oocyte donors?