Abstract P298: Association of Serum Sclerostin with Vascular Calcification in African Ancestry Men

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Allison L Kuipers ◽  
Iva Miljkovic ◽  
J Jeffery Carr ◽  
James G Terry ◽  
Cara S Nestlerode ◽  
...  
Keyword(s):  
Kidney Function ◽  
Vascular Calcification ◽  
Bone Mineralization ◽  
African Ancestry ◽  
Arterial Calcification ◽  
Serum Samples ◽  
Cross Sectional ◽  
P Values ◽  
Logistic Regression Models ◽  
Health History

Objective: Sclerostin, a Wnt pathway antagonist, is an established regulator of bone mineralization in humans but its potential importance in the regulation of vascular calcification is less clear. Therefore, our objective was to assess the relationship of serum sclerostin levels with coronary and aortic artery calcification (CAC and AAC, respectively) in African ancestry men on the island of Tobago. Methods: Detailed health history, clinical exam and computed tomography scans of CAC and AAC were obtained in 191 men aged ≥40 years (mean(SD): 62.9(8.0)years) recruited without regard to health status. Fasting serum samples were drawn and stored at -80°C until time of assay. Serum sclerostin levels were measured using ELISA according to manufacturer’s protocol (Biomedica Gruppe, Vienna, Austria). Multivariable logistic regression models were used to assess the cross-sectional association of sclerostin with prevalent arterial calcification. Results: In unadjusted analyses, the 57 of 191 (29.8%) of men with CAC were older, more likely to be hypertensive, had lower kidney function and had greater serum sclerostin (all P-values<0.05). The 131 of 191 (68.6%) of men with AAC were also older and more likely to be hypertensive, but they had greater total body fat and were more likely to be on statins, as well (all P-values<0.05). Mean(SD) sclerostin was 45.2 pmol/l (15.6 pmol/l). After adjusting for risk factors including age, physical and lifestyle characteristics, comorbidities, lipoproteins and kidney function, 1 SD greater sclerostin level was associated with 1.61-times (95%CI 1.02-2.53) greater odds of having CAC. Sclerostin was not associated with AAC in any model. Conclusions: This is the first study to show that, among African ancestry men, greater serum sclerostin levels were associated with CAC. In addition to its known role in bone mineralization, the Wnt antagonist, sclerostin, may also play a role in calcification of the coronary arteries.

scholarly journals Positive association between Brucella spp seroprevalences in livestock and humans from a cross-sectional study in Garissa and Tana River Counties, Kenya

2019 ◽  
Author(s):  
S.W. Kairu-Wanyoike ◽  
D. Nyamwaya ◽  
M. Wainaina ◽  
J. Lindahl ◽  
E. Ontiri ◽  
...  
Keyword(s):  
Regression Models ◽  
Cross Sectional Study ◽  
Mixed Effects ◽  
Sectional Study ◽  
Serum Samples ◽  
Cross Sectional ◽  
Logistic Regression Models ◽  
Household Level ◽  
Tana River ◽  
Seropositive Animal

AbstractBackgroundBrucella spp. is a zoonotic bacterial agent of high public health and socio-economic importance. It infects many species of animals including wildlife, and people may get exposed through direct contact with an infected animal or consumption of raw or undercooked animal products. We implemented a linked livestock-human cross-sectional study to determine seroprevalences and risk factors of Brucella spp. in livestock and humans. We also estimated intra-cluster correlation coefficients (ICCs) for these observations at the household and village levels.MethodologyThe study was implemented in Garissa County (specifically Ijara and Sangailu areas) and Tana River (Bura and Hola) counties. A household was the unit of analysis and the sample size was derived using the standard procedures. Serum samples were obtained from selected livestock and people from randomly selected households. Humans were sampled in both counties while livestock could be sampled only in Tana River County. Samples obtained were screened for anti-Brucella IgG antibodies using ELISA kits. Data were analyzed using generalized linear mixed effects logistic regression models with the household (herd) and village being used as random effects.ResultsThe overall seroprevalences were 3.47% (95% confidence interval [CI]: 2.72 – 4.36%) and 35.81% (95% CI: 32.87 – 38.84) in livestock and humans, respectively. In livestock, older animals and those sampled in Hola had significantly higher seroprevalences that younger ones or those sampled in Bura. Herd and village random effects were significant and ICC estimates associated with these variables were 0.40 (95% CI: 0.22 – 0.60) and 0.24 (95% CI: 0.08 – 0.52), respectively. For human data, older people, males, and people who lived in pastoral areas had significantly higher Brucella spp. seroprevalences than younger ones, females or those who lived in irrigated or riverine areas. People from households that had at least one seropositive animal were 3.35 (95% CI: 1.51 – 7.41) times more likely to be seropositive compared to those that did not. Human exposures significantly clustered at the household level; the ICC estimate obtained was 0.21 (95% CI: 0.06 – 0.52).ConclusionThe presence of a seropositive animal in a household significantly increased the risk of exposure in people in that household. Brucella spp. exposures in both livestock and humans clustered significantly at the household level. This suggests that risk-based surveillance measures, guided by locations of primary cases reported, either in humans or livestock, can be used to detect Brucella spp. infections livestock or humans, respectively.Author summaryBrucellosis is an important zoonotic disease that primarily affects livestock and wildlife. In humans, the disease is characterized by prolonged fever, body aches, joint pains and weakness while in livestock, the disease causes abortions and infertility. We carried out a study in northeastern Kenya (Garissa and Tana River Counties) to identify factors that affect the distribution of the disease in people and livestock. Livestock and people from randomly selected households were recruited and serum samples obtained for screening using anti-Brucella IgG ELISA kits to determine their Brucella spp. exposure. Data obtained were analyzed using mixed effects logistic regression models. Results obtained show that human and animal Brucella spp. seroprevalences cluster at the household level. The odds of exposure in humans were at least three times higher in households that had at least one seropositive animal compared to those that did not. These results can be used to design risk-based surveillance systems where each Brucella infection identified in livestock or humans could signal potential locations of other secondary infections.

Abstract 641: Protein Disulfide Isomerase-A1 Overexpression Enhances Vascular Calcification in Mice

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Luciana A Pescatore ◽  
Patricia Nolasco ◽  
Elisângela Farias-Silva ◽  
Leonardo Jensen ◽  
Carolina G Fernandes ◽  
...  
Keyword(s):  
Er Stress ◽  
Vascular Calcification ◽  
Protein Disulfide Isomerase ◽  
Arterial Calcification ◽  
Diabetic Patients ◽  
Cross Sectional ◽  
Disulfide Isomerase ◽  
Marker Expression ◽  
Protein Disulfide

Vascular calcification (VC) is an active pathophysiological process promoting enhanced morbidity and mortality without effective therapy. Oxidative stress and endoplasmic reticulum (ER) stress support cardiovascular calcification progression. We showed previously that the ER redox chaperone protein disulfide isomerase-A1 (PDI) is required for agonist-driven Nox NADPH oxidase activation. Oxidant levels and expression of Nox subunits and PDI are upregulated in calcifying rabbit valves. We hypothesized that PDI supports VC. We recently developed a new PDI overexpression mouse model (TgPDI) in FVB background (WT). To investigate whether TgPDI mice show increased VC, we challenged 20 week-old TgPDI mice with Vitamin-D 3 (VitD) for 14 days. Also, we incubated primary vascular smooth muscle cells (VSMC) isolated from WT or TgPDI mice with mineralizing medium (β-glycerophosphate 10mM + CaCl 2 6mM). TgPDI results were compared to those from respective WT littermates. We tested distinct VitD doses. At 9x10 4 IU/day, WT mice depicted negligible increases in calcification area (median 0.07% to 0.36% aorta cross-sectional area, p=ns, n=5), while TgPDI showed enhanced calcification (median 0.20 to 3.63 % area, p<0.05, n=4). The sum of calcification areas across all mice showed a 2.6-fold increase in TgPDI. TgPDI mice did not develop aortic valve stenosis or change in ascending aorta peak wave velocity at echocardiography. In vitro, VSMC phenotype marker expression (SM22 and alpha-actin) was enhanced in TgPDI vs. WT cells at baseline, while calcifying stimulation for 3 or 7 days decreased such VSMC marker expression both in WT and in TgPDI VSMC. Conversely, calcifying stimulation for 3 or 7 days showed no effects on ER stress marker expression (GRP78, GRP94). To assess whether these findings apply to humans, we examined femoral arteries from diabetic and non-diabetic patients with peripheral arterial disease, which showed increased arterial calcification and marked coincident PDI overexpression in samples from diabetic patients. In conclusion, PDI overexpression in vivo associates with enhanced VC after VitD calcifying stimulus. PDI and its associated signaling proteins deserve further study as potential therapeutic targets in VC progression.

Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans

Blood ◽  
2010 ◽  
Vol 115 (24) ◽  
pp. 5121-5123 ◽  
Author(s):  
Roger J. M. W. Rennenberg ◽  
Bernard J. van Varik ◽  
Leon J. Schurgers ◽  
Karly Hamulyak ◽  
Hugo ten Cate ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Vascular Calcification ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Cross Sectional Study ◽  
Matrix Gla Protein ◽  
Arterial Calcification ◽  
Cross Sectional

Abstract Vascular calcification is a marker of increased cardiovascular risk. Vitamin K–dependent matrix Gla protein (MGP) is important in inhibiting calcification. Because MGP activation is vitamin K dependent, we performed a cross-sectional study investigating the relationship between the use of vitamin K antagonists and extracoronary vascular calcification. From the Dutch thrombosis services we selected 19 patients younger than 55 years who had no other cardiovascular risk factors and who had used coumarins for more than 10 years, and compared these to 18 matched healthy controls. MGP was measured, and a plain x-ray of the thighs was taken to assess femoral arterial calcifications. The odds ratio for calcification in patients versus controls was 8.5 (95% confidence interval [CI] 2.01-35.95). Coumarin use and MGP were associated with calcification, even after adjusting for other risk factors. We conclude that long-term use of coumarins is associated with enhanced extracoronary vascular calcification, possibly through the inhibition of MGP carboxylation.

scholarly journals The Cell Origin and Role of Osteoclastogenesis and Osteoblastogenesis in Vascular Calcification

2021 ◽  
Vol 8 ◽  
Author(s):  
Wenhong Jiang ◽  
Zhanman Zhang ◽  
Yaodong Li ◽  
Chuanzhen Chen ◽  
Han Yang ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Bone Mineralization ◽  
Bone Matrix ◽  
Arterial Calcification ◽  
Arterial Walls ◽  
Large Numbers ◽  
Bone Matrix Proteins ◽  
A Cell ◽  
Mineral Resorption

Arterial calcification refers to the abnormal deposition of calcium salts in the arterial wall, which results in vessel lumen stenosis and vascular remodeling. Studies increasingly show that arterial calcification is a cell mediated, reversible and active regulated process similar to physiological bone mineralization. The osteoblasts and chondrocytes-like cells are present in large numbers in the calcified lesions, and express osteogenic transcription factor and bone matrix proteins that are known to initiate and promote arterial calcification. In addition, osteoclast-like cells have also been detected in calcified arterial walls wherein they possibly inhibit vascular calcification, similar to the catabolic process of bone mineral resorption. Therefore, tilting the balance between osteoblast-like and osteoclast-like cells to the latter maybe a promising therapeutic strategy against vascular calcification. In this review, we have summarized the current findings on the origin and functions of osteoblast-like and osteoclast-like cells in the development and progression of vascular progression, and explored novel therapeutic possibilities.

Evaluation of Serum Calprotectin Level and Disease Activity in Patients with Rheumatoid Arthritis

2019 ◽  
Vol 15 (4) ◽  
pp. 316-320
Author(s):  
Mir Amir Aghdashi ◽  
Seyedmostafa Seyedmardani ◽  
Sholeh Ghasemi ◽  
Zohre Khodamoradi
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Arthritis ◽  
Unknown Etiology ◽  
Tender Joint Count ◽  
Serum Samples ◽  
Tender Joint ◽  
Cross Sectional ◽  
Calprotectin Level ◽  
Remission Phase

Background: Rheumatoid Arthritis (RA) is the most common type of chronic inflammatory arthritis with unknown etiology marked by a symmetric, peripheral polyarthritis. Calprotectin also can be used as a biomarker of disease activity in inflammatory arthritis and other autoimmune diseases. Objective: In this study, we evaluated the association between serum calprotectin level and severity of RA activity. Methods: A cross-sectional study was conducted on 44 RA patients with disease flare-up. Serum samples were obtained from all patients to measure calprotectin, ESR, CRP prior to starting the treatment and after treatment period in the remission phase. Based on Disease Activity Score 28 (DAS28), disease activity was calculated. Results: Of 44 RA patients, 9(20.5%) were male and 35(79.5%) were female. The mean age of our cases was 53±1.6 years. Seventeen (38.6%) patients had moderate DAS28 and 27(61.4%) had high DAS28. The average level of calprotectin in the flare-up phase was 347.12±203.60 ng/ml and 188.04±23.58 ng/ml in the remission phase. We did not find any significant association between calprotectin and tender joint count (TJC; P=0.22), swollen joint count (SJC; P=0.87), and general health (GH; P=0.59), whereas significant associations were found between the calprotectin level and ESR (p=0.001) and DAS28 (p=0.02). The average calprotectin level in moderate DAS28 (275.21±217.96 ng/ml) was significantly lower than that in high DAS28 (392.4±183.88 ng/ml) (p=0.05). Conclusion: We showed that the serum level of calprotectin can be a useful and reliable biomarker in RA activity and its severity. It also can predict treatment response.

P1237TISSUE-NONSPECIFIC ALKALINE PHOSPHATASE, A CULPRIT DURING ARTERIAL MEDIA CALCIFICATION BUT INDISPENSABLE DURING PHYSIOLOGICAL BONE FORMATION/-MINERALIZATION IN RATS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Britt Opdebeeck ◽  
José Millan Luis ◽  
Anthony Pinkerton ◽  
Anja Verhulst ◽  
Patrick D'Haese ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Formation ◽  
Vascular Calcification ◽  
Rat Model ◽  
Bone Mineralization ◽  
Calcium Content ◽  
Marker Genes ◽  
Peripheral Arteries ◽  
Calcium Phosphorus ◽  
Chondrogenic Marker

Abstract Background and Aims Vascular media calcification is frequently seen in elderly and patients with chronic kidney disease (CKD), diabetes and osteoporosis. Pyrophosphate is a well-known calcification inhibitor that binds to nascent hydroxyapatite crystals and prevents further incorporation of inorganic phosphate into these crystals. However, the enzyme tissue-nonspecific alkaline phosphatase (TNAP), which is highly expressed in calcified arteries, degrades extracellular pyrophosphate into phosphate ions, by which pyrophosphate loses its ability to block vascular calcification. Here, we aimed to evaluate whether a TNAP inhibitor is able to prevent the development of arterial calcification in a rat model of warfarin-induced vascular calcification. Method To induce vascular calcification, rats received a diet containing 0.30% warfarin and 0.15% vitamin K1 throughout the entire study and were subjected to the following daily treatments: (i) vehicle (n=10) or (ii) 10 mg/kg/day TNAP-inhibitor (n=10) administered via an intraperitoneal catheter from start of the study until sacrifice at week 7. Calcium, phosphorus and parathyroid hormone (PTH) levels were determined in serum samples as these are important determinants of vascular calcification. As TNAP is also expressed in the liver, serum alanine aminotransferase (ALT) and aspartate (AST) levels were analyzed. At sacrifice, vascular calcification was evaluated by measurement of the total calcium content in the arteries and quantification of the area % calcification on Von Kossa stained sections of the aorta. The mRNA expression of osteo/chondrogenic marker genes (runx2, TNAP, SOX9, collagen 1 and collagen 2) was analyzed in the aorta by qPCR to verify whether vascular smooth muscle cells underwent reprogramming towards bone-like cells. Bone histomorphometry was performed on the left tibia to measure static and dynamic bone parameters as TNAP also regulates physiological bone mineralization. Results No differences in serum calcium, phosphorus and PTH levels was observed between both study groups. Warfarin exposure resulted in distinct calcification in the aorta and peripheral arteries. Daily dosing with the TNAP inhibitor (10 mg/kg/day) for 7 weeks significantly reduced vascular calcification as indicated by a significant decrease in calcium content in the aorta (vehicle 3.84±0.64 mg calcium/g wet tissue vs TNAP inhibitor 0.70±0.23 mg calcium/g wet tissue) and peripheral arteries and a distinct reduction in area % calcification on Von Kossa stained aortic sections as compared to vehicle condition. The inhibitory effects of SBI-425 on vascular calcification were without altering serum liver markers ALT and AST levels. Furthermore, TNAP-inhibitor SBI-425 did not modulate the mRNA expression of osteo/chondrogenic marker genes runx2, TNAP, SOX9, collagen 1 and 2. Dosing with SBI-425 resulted in decreased bone formation rate and mineral apposition rate, and increased osteoid maturation time and this without significant changes in osteoclast- and eroded perimeter. Conclusion Dosing with TNAP inhibitor SBI-425 significantly reduced the calcification in the aorta and peripheral arteries of a rat model of warfarin-induced vascular calcification and this without affecting liver function. However, suppression of TNAP activity should be limited in order to maintain adequate physiological bone mineralization.

scholarly journals Association between Physical Activity and Comorbidities in Spanish People with Asthma-COPD Overlap

2021 ◽  
Vol 13 (14) ◽  
pp. 7580
Author(s):  
Sheila Sánchez Castillo ◽  
Lee Smith ◽  
Arturo Díaz Suárez ◽  
Guillermo Felipe López Sánchez
Keyword(s):  
Physical Activity ◽  
Short Form ◽  
National Health Survey ◽  
Lumbar Pain ◽  
Chronic Obstructive ◽  
Cross Sectional ◽  
Obstructive Pulmonary Disease ◽  
Logistic Regression Models ◽  
Adjusted Model ◽  
Activity Questionnaire

Asthma and chronic obstructive pulmonary disease (COPD) are important conditions which often coexist. Higher rates of comorbidities among people with asthma-COPD overlap (ACO) may complicate clinical management. The aim of this study was to determine the prevalence of 30 different comorbidities and to analyze associations between these comorbidities and physical activity (PA) in Spanish people with ACO. Cross-sectional data from the Spanish National Health Survey 2017 were analyzed. A total of 198 Spanish people with ACO aged 15–69 years (60.6% women) were included in this study. PA was measured with the International Physical Activity Questionnaire (IPAQ) short form. Diagnosis of chronic conditions were self-reported. Associations between PA and comorbidities were analyzed using multivariable logistic regression models. The most prevalent comorbidities were chronic allergy (58.1%), chronic lumbar pain (42.4%), chronic cervical pain (38.4%), hypertension (33.3%) and arthrosis (31.8%). A PA level lower than 600 MET·min/week was significantly associated with urinary incontinence (OR = 3.499, 95% CI = 1.369–8.944) and osteoporosis (OR = 3.056, 95% CI = 1.094–8.538) in the final adjusted model. Therefore, the potential influence of PA on reducing the risk of these conditions among people with ACO should be considered, not only because of the health benefits, but also because PA can contribute to a more sustainable world.

scholarly journals The number of household members as a risk factor for peptic ulcer disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mi Hong Yim ◽  
Keun Ho Kim ◽  
Bum Ju Lee
Keyword(s):  
Peptic Ulcer ◽  
Peptic Ulcer Disease ◽  
Binary Logistic Regression ◽  
Cross Sectional Study ◽  
Living Alone ◽  
Cross Sectional ◽  
Ulcer Disease ◽  
Logistic Regression Models ◽  
Household Members ◽  
H Pylori

AbstractPeptic ulcer disease (PUD) is caused by many sociodemographic and economic risk factors other than H. pylori infection. However, no studies reported an association between PUD and the number of household members. We showed the number of family members affected by PUD based on sex in a Korean population. This cross-sectional study used 1998–2009 data from the Korea National Health and Nutrition Examination Survey of the Korea Centers for Disease Control and Prevention. Multiple binary logistic regression models adjusted for confounders were constructed to analyze the association of PUD with the number of household members. The number of household members was associated with PUD, age, body mass index (BMI), waist circumference, systolic blood pressure, hemoglobin, glucose, location (urban/rural), income, education level, stress, current drinking, and smoking in both sexes. Men with other household members had a higher PUD risk compared to men or women living alone (reference), and the opposite was observed for women. Men with 4 household members had a higher PUD risk than men living alone in the model adjusted for age, BMI, income, location, education, and stress (OR = 2.04 [95% CI 1.28–3.27], p value = .003). Women with more than 6 household members had a lower PUD risk than women living alone in the adjusted model (OR = 0.50 [0.33–0.75], p value = .001). Women with more household members had a lower PUD risk. However, more men had PUD than women regardless of the number of household members.

scholarly journals Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms

2020 ◽  
Author(s):  
Richard C Gerkin ◽  
Kathrin Ohla ◽  
Maria G Veldhuizen ◽  
Paule V Joseph ◽  
Christine E Kelly ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Respiratory Symptom ◽  
Respiratory Illness ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Logistic Regression Models ◽  
Olfactory Loss ◽  
Visual Analog Scales ◽  
Cardinal Symptoms ◽  
Smell Loss

Abstract In a preregistered, cross-sectional study we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points; C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC=0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4&lt;OR&lt;10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.

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