Adipose tissue is associated with kidney function parameters.

Obesity is characterized by the accumulation of adipose tissue in different body compartments. Whether adipose tissue directly affects kidney function is still unknown. We aimed to investigate the role of the adipose tissue and circulating creatinine, cystatin C and kidney function in subjects free of cardio-renal diseases. In the KORA-MRI population-based study, 377 subjects (mean age 56.2 ± 9.2 years; 41.6% female) underwent whole-body 3T-MRI examination. Adipose tissue defined as visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were quantified from T1-DIXON sequence using a semi-automatic algorithm. Serum creatinine and cystatin C were measured using standard laboratory and estimated glomerular filtration rate (e-GFR) was performed based on creatinine (e-GFRcrea), cystatin C (e-GFRcys) and creatinine-cystatin C (e-GFRcc). Linear regression analysis, adjusted for risk factors, was used to investigate the relationship between adipose tissue and circulating creatinine, cystatin C, and kidney function. In multivariate analyses VAT was inversely associated with eGFRcys (ß = - 4.88, p = < 0.001), and positively associated with serum cystatin C (ß = 0.05, p = < 0.001), respectively. No association was found between other adipose parameters such as total adipose tissue (TAT) and subcutaneous adipose tissue (SAT) and serum creatinine, urine microalbumin and eGFRcrea. Stratified analyses according to BMI revealed confirmatory results for category of BMI > 30. VAT is positively associated with serum cystatin C and inversely with eGFR based on cystatin C, suggesting a direct involvement of visceral adipose tissue in increased metabolism of cystatin C and consequently decreased kidney function.

Metabolic Syndrome and Breast Cancer Molecular Subtypes: An Observational Patient Study.

Background: Breast cancer molecular subtypes share various prognostic profiles, and luminal A molecular subtypes have a better prognosis compared with other molecular subtypes. However, whether metabolic syndrome or individual risk factors of metabolic syndrome influence on the development of molecular subtype remains elusive. We aimed to assess the association between metabolic syndrome risk factors and breast cancer molecular subtypes among patients with metabolic syndrome in a clinical setting. Methods: In total, 101 breast cancer patients with mean age, 58.4 ± 8.5 years, and overt metabolic syndrome prospectively were recruited. Immunohistochemistry procedure was used to determine molecular subtypes. Assessment of clinical, biochemical, and anthropometric parameters was performed. Logistic regression analysis was used to assess the relationship between risk factors and breast cancer molecular subtypes categories. A similar approach was used to assess the relation between breast cancer molecular subtypes and menopause. Results: Comparison of metabolic syndrome individual risk factors according to breast cancer molecular subtypes no statistical difference was found for systolic (P = .33) and diastolic blood pressure (P = .17), fasting glucose (P = .77), triglycerides (P = .62), high-density lipoprotein (P = .33), body mass index (P = .87), and waist circumference (P = .81). A positive trend was found between high-density lipoprotein and HER2+. No association was found with other risk factors. Moreover, an association was found between HER2+ categories and menopause. Conclusion: In breast cancer patients with metabolic syndrome, we observed an increased trend between high-density lipoprotein and HER2+ molecular subtype, suggesting that underlying dyslipidemia may favor poor prognosis. HER2+ was associated with menopause which may influence further expression of HER2+ .

Central hemodynamics in relation to blood lead in young men prior to chronic occupational exposure.

Background: Aortic pulse wave velocity (aPWV) predicts cardiovascular complications, but the association of central arterial properties with blood lead level (BL) is poorly documented. We therefore assessed their association with BL in 150 young men prior to occupational lead exposure, using baseline data of the Study for Promotion of Health in Recycling Lead (NCT02243904). Methods: Study nurses administered validated questionnaires and performed clinical measurements. Venous blood samples were obtained after 8-12 h of fasting. The radial, carotid and femoral pulse waves were tonometrically recorded. We accounted for ethnicity, age, anthropometric characteristics, mean arterial pressure, heart rate, smoking and drinking, and total and high-density lipoprotein serum cholesterol, as appropriate. Results: Mean values were 4.14 µg/dL for BL, 27 years for age, 108/79/28 mm Hg for central systolic/diastolic/pulse pressure, 100/10% for the augmentation ratio/index, 1.63 for pressure amplification, 5.94 m/s for aPWV, 27/11 mm Hg for the forward/backward pulse pressure height, and 43% for the reflection index. Per 10-fold BL increase, central diastolic pressure and the augmentation ratio were respectively 5.37 mm Hg (95% confidence interval [CI], 1.00-9.75) and 1.57 (CI, 0.20-2.94) greater, whereas central pulse pressure and the forward pulse pressure height were 3.74 mm Hg (CI, 0.60-6.88) and 3.37 mm Hg (CI, 0.22-6.53) smaller (p ≤ .036 for all). The other hemodynamic measurements were unrelated to BL. The reflected pulse peak time was inversely correlated with diastolic pressure (r = -0.20; p ≤ .017). Conclusion: At the exposure levels observed in our current study, aPWV, the gold standard to assess arterial stiffness, was not associated with BL. Increased peripheral arterial resistance, as reflected by higher diastolic pressure, might bring reflection points closer to the heart, thereby moving the backward wave into systole and increasing the augmentation ratio in relation to BL.

Neurocognitive function in relation to blood lead among young men prior to chronic occupational exposure.

Objectives Higher than contemporary exposure levels and advanced age of study participants have limited the interpretation of previous studies relating neurocognitive function to lead exposure. We reassessed this association in young American men prior to chronic occupational exposure at lead recycling plants, using baseline measurements of the Study for Promotion of Health in Recycling Lead (NCT02243904). Methods We administered the Stroop test (ST) and the digit-symbol test (DST) to 339 men (mean age, 28.6 years; participation rate 82.7%). Whole blood lead (BL) was determined by inductively coupled plasma mass spectrometry and related ST and DST test results using multivariable-adjusted regression. Results Average values were 4.26 µg/dL for BL, 1624 ms and 1474 ms for mean reaction time in incongruent and congruent ST trials, and 109 sec for mean total latency in DST. The number of participants with fully correct answers amounted to 281 (82.9%) and 334 (98.5%) in incongruent and congruent ST trials, respectively, and to 198 (58.4%) in the DST. In multivariable-adjusted analyses, there was no association between cognitive performance and BL except for a weak but opposite association in DST; for a 10-fold BL increment, mean total latency was 5.4% (95% confidence interval, -0.4‒11.5%; P=0.066) higher, whereas the error score was 42% (-10‒69%; P=0.096) lower. To exclude an effect of the cumulative lead dose, sensitivity analyses restricted to workers <40, 35 and 30 years were confirmatory. Conclusions At the exposure levels in our current study, we failed to demonstrate a consistent inverse association of BL with neurocognitive performance in young American men.

Renal function in relation to low-level environmental lead exposure.

BACKGROUND: Numerous studies suggested that occupational or environmental exposure to lead adversely affects renal function. However, most studies lost relevance because of the substantially lower current environmental lead exposure and all relied on serum creatinine to estimate glomerular filtration. We investigated the association of estimated glomerular filtration rate (eGFR), estimated from serum creatinine, cystatin C or both, with blood lead (BPb) using the baseline measurements of the ongoing Study for Promotion of Health in Recycling Lead (SPHERL; NCT02243904) in newly hired workers prior to significant occupational lead exposure. METHODS: Among 447 men (participation rate, 82.7%), we assessed the association of eGFR and the urinary albumin-to-creatinine ratio (ACR) with BPb across thirds of the BPb distribution using linear regression analysis. Fully adjusted models accounted for age, blood pressure, body mass index, the waist-to-hip ratio, smoking, the total-to-high-density-lipoprotein ratio, plasma glucose, serum γ-glutamyltransferase and antihypertensive drug treatment. RESULTS: Age averaged 28.7 (SD, 10.2) years (range, 19.1-31.8). Geometric mean BPb concentration was 4.34 µg/dL (5th-95th percentile interval, 0.9-14.8). In unadjusted and adjusted analyses, eGFR estimated from serum creatinine [mean (SD), 105.26 (15.2) mL/min/1.73 m2], serum cystatin C [mean (SD), 127.8 (13.8) mL/min/1.73 m2] or both [mean (SD), 111.9 (14.8) mL/min/1.73 m2] was not associated with BPb (P ≥ 0.36), whereas ACR [geometric mean, 4.32 mg/g (5th-95th percentile interval, 1.91-12.50)] was lower with higher BPb. CONCLUSIONS: At the BPb levels observed in this study, there was no evidence for an association between renal function and lead exposure.

Conventional and Ambulatory Blood Pressure as Predictors of Diastolic Left Ventricular Function in a Flemish Population.

BACKGROUND: No longitudinal study compared associations of echocardiographic indexes of diastolic left ventricular function studies with conventional (CBP) and daytime ambulatory (ABP) blood pressure in the general population. METHODS AND RESULTS: In 780 Flemish (mean age, 50.2 years; 51.7% women), we measured left atrial volume index (LAVI), peak velocities of the transmitral blood flow (E) and mitral annular movement (e') in early diastole and E/e' 9.6 years (median) after CBP and ABP. In adjusted models including CBP and ABP, we expressed associations per 10/5-mm Hg systolic/diastolic blood pressure increments. LAVI and E/e' were 0.65/0.40 mL/m2 and 0.17/0.09 greater with higher systolic/diastolic ABP (P≤0.028), but not with higher baseline CBP (P≥0.086). e' was lower (P≤0.032) with higher diastolic CBP (-0.09 cm/s) and ABP (-0.19 cm/s). When we substituted baseline CBP by CBP recorded concurrently with echocardiography, LAVI and E/e' remained 0.45/0.38 mL/m2 and 0.15/0.08 greater with baseline ABP (P≤0.036), while LAVI (+0.53 mL/m2) and E/e' (+0.19) were also greater (P<0.001) in relation to concurrent systolic CBP. In categorized analyses of baseline data, sustained hypertension or masked hypertension compared with normotension or white-coat hypertension was associated with greater LAVI (24.0 versus 22.6 mL/m2) and E/e' (7.35 versus 6.91) and lower e' (10.7 versus 11.6 cm/s; P≤0.006 for all) with no differences (P≥0.092) between normotension and white-coat hypertension or between masked hypertension and sustained hypertension. CONCLUSIONS: ABP is a long-term predictor of diastolic left ventricular function, statistically outperforming distant but not concurrent CBP. Masked hypertension and sustained hypertension carry equal risk for deterioration of diastolic left ventricular function.

Association of office and ambulatory blood pressure with blood lead in workers before occupational exposure.

In view of decreasing lead exposure and guidelines endorsing ambulatory above office blood pressure (BP) measurement, we reassessed association of BP with blood lead (BL) in 236 newly employed men (mean age, 28.6 years) without previous lead exposure not treated for hypertension. Office BP was the mean of five auscultatory readings at one visit. Twenty-four-hour BP was recorded at 15- and 30-minute intervals during wakefulness and sleep. BL was determined by inductively coupled plasma mass spectrometry. Systolic/diastolic office BP averaged 120.0/80.7 mm Hg, and the 24-hour, awake, and asleep BP 125.5/73.6, 129.3/77.9, and 117.6/65.0 mm Hg, respectively. The geometric mean of blood lead was 4.5 µg/dL (interquartile range, 2.60-9.15 µg/dL). In multivariable-adjusted analyses, effect sizes associated with BL doubling were 0.79/0.87 mm Hg (P = .11/.043) for office BP and 0.29/-0.25, 0.60/-0.10, and -0.40/-0.43 mm Hg for 24-hour, awake, and asleep BP (P ≥ .33). Neither office nor 24-hour ambulatory hypertension was related to BL (P ≥ .14). A clinically relevant white coat effect (WCE; office minus awake BP, ≥20/≥10 mm Hg) was attributable to exceeding the systolic or diastolic threshold in 1 and 45 workers, respectively. With BL doubling, the systolic/diastolic WCE increased by 0.20/0.97 mm Hg (P = .57/.046). Accounting for the presence of a diastolic WCE, reduced the association size of office diastolic BP with BL to 0.39 mm Hg (95% confidence interval, -0.20 to 1.33; P = .15). In conclusion, a cross-sectional analysis of newly hired workers before lead exposure identified the WCE as confounder of the association between office BP and BL and did not reveal any association between ambulatory BP and BL.

Associations of Endogenous Estradiol and Testosterone Levels With Plaque Composition and Risk of Stroke in Subjects With Carotid Atherosclerosis.

RATIONALE: Sex steroids may play a role in plaque composition and in stroke incidence. OBJECTIVES: To study the associations of endogenous estradiol and testosterone with carotid plaque composition in elderly men and postmenopausal women with carotid atherosclerosis, as well as with risk of stroke in this population. METHODS AND RESULTS: Data of 1023 postmenopausal women and 1124 men (≥45 years) with carotid atherosclerosis, from prospective population-based RS (Rotterdam Study), were available. At baseline, total estradiol (TE) and total testosterone (TT) were measured. Carotid atherosclerosis was assessed by ultrasound, whereas plaque composition (presence of calcification, lipid core, and intraplaque hemorrhage) was assessed by magnetic resonance imaging. TE and TT were not associated with calcified carotid plaques in either sex. TE was associated with presence of lipid core in both sexes (in women odds ratio, 1.48 [95% confidence interval [CI], 1.02-2.15]; in men odds ratio, 1.23 [95% CI, 1.03-1.46]), whereas no association was found between TT and lipid core in either sex. Higher TE (odds ratio, 1.58 [95% CI, 1.03-2.40]) and lower TT (odds ratio, 0.82 [95% CI, 0.68-0.98]) were associated with intraplaque hemorrhage in women but not in men. In women, TE was associated with increased risk of stroke (hazard ratio, 1.98 [95% CI, 1.01-3.88]), whereas no association was found in men. TT was not associated with risk of stroke in either sex. CONCLUSIONS: TE was associated with presence of vulnerable carotid plaque as well as increased risk of stroke in women, whereas no consistent associations were found for TT in either sex.