Soluble Klotho and Incident Hypertension

2021 ◽  
Vol 16 (10) ◽  
pp. 1502-1511
Author(s):  
David A. Drew ◽  
Ronit Katz ◽  
Stephen Kritchevsky ◽  
Joachim H. Ix ◽  
Michael G. Shlipak ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Confidence Interval ◽  
Disease Risk ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Cross Sectional ◽  
Baseline Serum ◽  
Content Type ◽  
Incident Hypertension ◽  
Body Composition Study

Background and objectivesHypertension is associated with significant morbidity and mortality despite effective antihypertensive therapies. Soluble klotho is a circulating protein that in preclinical studies is protective against the development of hypertension. There are limited studies of klotho and blood pressure in humans.Design, setting, participants, & measurementsWithin the Health, Aging, and Body Composition Study, a cohort of well-functioning older adults, soluble klotho was measured in serum. We evaluated the cross-sectional and longitudinal association between klotho and blood pressure, prevalent hypertension, incident hypertension, and BP trajectories. Analyses were adjusted for demographics, cardiovascular disease and kidney disease risk factors, and measures of mineral metabolism including calcium, phosphate, parathyroid hormone, 25(OH) vitamin D, and fibroblast growth factor 23.ResultsThe median klotho concentration was 630 pg/ml (478–816, 25th to 75th percentile). Within the cohort, 2093 (76%) of 2774 participants had prevalent hypertension and 476 (70%) of the remaining 681 developed incident hypertension. There was no association between klotho and prevalent hypertension or baseline systolic BP, but higher klotho was associated with higher baseline diastolic BP (fully adjusted β=0.92 mmHg, 95% confidence interval, 0.24 to 1.60 mmHg, higher per two-fold higher klotho). Higher baseline serum klotho levels were significantly associated with a lower rate of incident hypertension (fully adjusted hazard ratio, 0.80; 95% confidence interval, 0.69 to 0.93 for every two-fold higher klotho). Higher klotho was also associated with lower subsequent systolic BP and diastolic BP (−0.16, 95% confidence interval, −0.31 to −0.01, mmHg lower systolic BP per year and −0.10, 95% confidence interval, −0.18 to −0.02, mmHg lower diastolic BP per year, for each two-fold higher klotho).ConclusionsHigher klotho is associated with higher baseline diastolic but not systolic BP, a lower risk of incident hypertension, and lower BP trajectories during follow-up.

scholarly journals Relationship between Dietary n-6 Fatty Acid Intake and Hypertension: Effect of Glycated Hemoglobin Levels

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1825 ◽  
Author(s):  
Haruki Nakamura ◽  
Akinori Hara ◽  
Hiromasa Tsujiguchi ◽  
Thao Thi Thu Nguyen ◽  
Yasuhiro Kambayashi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Glycated Hemoglobin ◽  
Cross Sectional Study ◽  
Fatty Acid Intake ◽  
Cross Sectional ◽  
Acid Intake

The relationship between dietary n-6 fatty acids and hypertension is not clear. The metabolic products of n-6 fatty acids include those that control blood pressure, such as prostaglandin and thromboxane, and that differ depending on the extent of glucose tolerance. This cross-sectional study investigated the association of dietary n-6 fatty acid intake on hypertension, and the effects of glycated hemoglobin (HbA1c) value in 633 Japanese subjects aged 40 years and older. Dietary intake was measured using a validated brief self-administered diet history questionnaire. We defined hypertension as the use of antihypertensive medication or a blood pressure of 140/90 mmHg. The prevalence of hypertension was 55.3%. A high n-6 fatty acids intake inversely correlated with hypertension in subjects with HbA1c values less than 6.5% (odds ratio, 0.857; 95% confidence interval, 0.744 to 0.987). On the contrary, in subjects with an HbA1c value of 6.5% or higher, the n-6 fatty acids intake was significantly associated with hypertension (odds ratio, 3.618; 95% confidence interval, 1.019 to 12.84). Regular dietary n-6 fatty acid intake may contribute to the prevention and treatment of hypertension in a healthy general population. By contrast, in subjects with diabetes, regular n-6 fatty acids intake may increase the risk of hypertension.

scholarly journals Fibroblast Growth Factor 23 and Blood Pressure in Older Adults

Hypertension ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 236-243
Author(s):  
David A. Drew ◽  
Ronit Katz ◽  
Stephen Kritchevsky ◽  
Joachim H. Ix ◽  
Michael G. Shlipak ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Older Adults ◽  
Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Antihypertensive Medications ◽  
Incident Hypertension ◽  
Blood Pressures ◽  
The Mean ◽  
Fgf 23

FGF-23 (fibroblast growth factor 23) regulates phosphorus and vitamin D. Elevated FGF-23 is associated with incident hypertension in young- and middle-aged adults, but there is limited data in older adults. Serum FGF-23 was measured using an intact ELISA assay in 2496 participants of the Healthy Aging and Body Composition Study. The association between FGF-23 and prevalent hypertension (self-reported and confirmed by use of antihypertensive medications) and number of antihypertensive medications was determined. The associations between FGF-23 and incident hypertension, and diastolic and systolic blood pressure trajectories were evaluated over 10 years. Models were adjusted for demographics, estimated glomerular filtration rate and albuminuria, cardiovascular disease risk factors, and measures of mineral metabolism. The mean (SD) age was 75 (3) years, with 51% women, and 40% black participants. The prevalence of hypertension at baseline was 75% and the mean systolic and diastolic blood pressures were 134 (21) mm Hg and 70 (12) mm Hg, respectively. The majority of participants without hypertension at baseline developed incident hypertension (576 of 1109 or 52%). In adjusted models, each 2-fold higher FGF-23 was associated with prevalent baseline hypertension (odds ratio=1.46 [1.24–1.73]) and greater number of blood pressure medications (IRR=1.14 [1.08–1.21]) but not with baseline diastolic or systolic blood pressure. In fully adjusted longitudinal analyses, a 2-fold higher FGF-23 was associated with incident hypertension (hazard ratio=1.18 [1.03–1.36]) and worsening systolic blood pressures (β=0.24 [0.08–0.40] mm Hg per year increase), but not with diastolic blood pressures (β=0.04 [−0.04 to 0.12] mm Hg per year increase). Higher FGF-23 concentrations are associated with prevalent and incident hypertension as well as rising systolic blood pressures in community-living older adults.

scholarly journals Heterogeneous Exposure Associations in Observational Cohort Studies: The Example of Blood Pressure in Older Adults

2019 ◽  
Vol 189 (1) ◽  
pp. 55-67
Author(s):  
Michelle C Odden ◽  
Andreea M Rawlings ◽  
Abtin Khodadadi ◽  
Xiaoli Fern ◽  
Michael G Shlipak ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Older Adults ◽  
Confidence Interval ◽  
Systolic Blood Pressure ◽  
Cardiovascular Health ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Creatinine Concentration ◽  
Body Composition Study ◽  
Health Aging

Abstract Heterogeneous exposure associations (HEAs) can be defined as differences in the association of an exposure with an outcome among subgroups that differ by a set of characteristics. In this article, we intend to foster discussion of HEAs in the epidemiologic literature and present a variant of the random forest algorithm that can be used to identify HEAs. We demonstrate the use of this algorithm in the setting of the association between systolic blood pressure and death in older adults. The training set included pooled data from the baseline examination of the Cardiovascular Health Study (1989–1993), the Health, Aging, and Body Composition Study (1997–1998), and the Sacramento Area Latino Study on Aging (1998–1999). The test set included data from the National Health and Nutrition Examination Survey (1999–2002). The hazard ratios ranged from 1.25 (95% confidence interval: 1.13, 1.37) per 10-mm Hg increase in systolic blood pressure among men aged ≤67 years with diastolic blood pressure greater than 80 mm Hg to 1.00 (95% confidence interval: 0.96, 1.03) among women with creatinine concentration ≤0.7 mg/dL and a history of hypertension. HEAs have the potential to improve our understanding of disease mechanisms in diverse populations and guide the design of randomized controlled trials to control exposures in heterogeneous populations.

Abstract P122: The Identification Of New Serum Uric Acid Levels Cut-off Point To Prevent Prehypertension And Hypertension Based On Jnc 7 And Acc/aha 2017 Classification: A Cross-sectional Study

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Mochammad Sja'bani ◽  
Lucky Aziza Bawazier ◽  
Fredie Irijanto ◽  
Zulaela Zulaela ◽  
Agus Widiatmoko ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Uric Acid ◽  
Confidence Interval ◽  
Serum Uric Acid ◽  
Simple Random Sampling ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
History Of ◽  
Stage 1

Background: Serum uric acid levels have been reported to be associated with elevated blood pressure and hypertension events. It is needed to determine the prognostic serum uric acid (SUA) cut-off point to prevent the incidents of prehypertension and hypertension. Methods: This was a cross-sectional study involving a total of 733 participants who a had history of prehypertension in 2007. These participants were selected from “Mlati Study Database” in 2007 by simple random sampling using statistical software. Participants underwent both physical and laboratorical examination. Data were analyzed based on JNC 7 and ACC/AHA 2017 guideline. Results: Based on JNC 7 classification, the analysis using ROC curve showed that the prognostic SUA cut-off point of 4.85 mg/dL was able to indicate the incidents of prehypertension or hypertension in the database (95% confidence interval, CI, 0.532-0.629, p=0.001). Additional analysis using ACC/AHA 2017 guideline as the blood pressure classification was also performed for comparison. Based on ACC/AHA 2017 classification, the ROC curved showed a slightly higher SUA cut-off points than the previous analysis using JNC 7. The prognostic SUA cut-off point of 4.95 mg/dL was able to indicate the events of hypertension stage 1 and stage 2 in the database (95% confidence interval, CI, 0.532-0.615, p=0.001). These results were parallel with the previous study which reported that SUA cut-off points of 5-7 mg/dL (high-normal SUA) and ≥7 mg/dL (high SUA) were associated with the incidents of prehypertension and hypertension. Conclusion: The new SUA cut-off points may be used as an early warning for the development of prehypertension and hypertension in the future.

Organizational Characteristics Associated with High Performance in Medicare’s Comprehensive End-Stage Renal Disease Care Initiative

2021 ◽  
Vol 16 (10) ◽  
pp. 1522-1530
Author(s):  
Kelsey M. Drewry ◽  
Amal N. Trivedi ◽  
Adam S. Wilk
Keyword(s):  
Confidence Interval ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Standardized Mortality Ratio ◽  
Marginal Effect ◽  
Cross Sectional ◽  
Content Type ◽  
Percentage Points ◽  
Stage Renal Disease ◽  
End Stage

Background and objectivesMedicare plans to extend financial structures tested through the Comprehensive End-Stage Renal Disease Care (CEC) Initiative—an alternative payment model for maintenance dialysis providers—to promote high-value care for beneficiaries with kidney failure. The End-Stage Renal Disease Seamless Care Organizations (ESCOs) that formed under the CEC Initiative varied greatly in their ability to generate cost savings and improve patient health outcomes. This study examined whether organizational or community characteristics were associated with ESCOs’ performance.Design, setting, participants, & measurementsWe used a retrospective pooled cross-sectional analysis of all 37 ESCOs participating in the CEC Initiative during 2015–2018 (n=87 ESCO-years). Key exposures included ESCO characteristics: number of dialysis facilities, number and types of physicians, and years of CEC Initiative experience. Outcomes of interest included were above versus below median gross financial savings (2.4%) and standardized mortality ratio (0.93). We analyzed unadjusted differences between high- and low-performing ESCOs and then used multivariable logistic regression to construct average marginal effect estimates for parameters of interest.ResultsAbove-median gross savings were obtained by 23 (52%) ESCOs with no program experience, 14 (32%) organizations with 1 year of experience, and seven (16%) organizations with 2 years of experience. The adjusted likelihoods of achieving above-median gross savings were 23 (95% confidence interval, 8 to 37) and 48 (95% confidence interval, 24 to 68) percentage points higher for ESCOs with 1 or 2 years of program experience, respectively (versus none). The adjusted likelihood of achieving above-median gross savings was 1.7 (95% confidence interval, −3 to −1) percentage points lower with each additional affiliated dialysis facility. Adjusted mortality rates were lower for ESCOs located in areas with higher socioeconomic status.ConclusionsSmaller ESCOs, organizations with more experience in the CEC Initiative, and those located in more affluent areas performed better under the CEC Initiative.

Higher cardiorespiratory fitness attenuates arterial stiffening associated with the Ala54Thr polymorphism in FABP2

2013 ◽  
Vol 45 (6) ◽  
pp. 237-242 ◽  
Author(s):  
Shumpei Fujie ◽  
Motoyuki Iemitsu ◽  
Haruka Murakami ◽  
Kiyoshi Sanada ◽  
Hiroshi Kawano ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Cardiorespiratory Fitness ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
Peak Oxygen Uptake ◽  
Cross Sectional ◽  
Fatty Acid Binding

Fatty acid binding protein 2 (FABP2) Ala54Thr polymorphism is a candidate gene associated with the risk of cardiovascular disease. Habitual exercise brings higher cardiorespiratory fitness and results in the improvement of cardiovascular disease risk. However, the effect of cardiorespiratory fitness level and FABP2 Ala54Thr polymorphism on the risk of cardiovascular diseases remains unclear. In the present study, a cross-sectional investigation of 837 Japanese men and women was performed to clarify the effects of cardiorespiratory fitness on the relationship between risk of cardiovascular disease and FABP2 Ala54Thr gene polymorphism. The study subjects were divided into high-cardiorespiratory fitness (High-Fit) and low-cardiorespiratory fitness (Low-Fit) groups based on the median value of peak oxygen uptake in each sex and decade. The FABP2 Ala54Thr polymorphism did not significantly affect carotid β-stiffness or blood pressure. In the Low-Fit group, carotid β-stiffness, systolic blood pressure, and diastolic blood pressure were higher for individuals with the Ala/Ala genotype compared with those with the Ala/Thr or Thr/Thr genotype, whereas no differences were observed in the High-Fit group. Additionally, serum triglyceride and plasma glucose levels were lower and serum high-density lipoprotein cholesterol levels were higher in the High-Fit group compared with the Low-Fit group; the FABP2 Ala54Thr polymorphism did not significantly affect these parameters. These results suggest that the higher cardiorespiratory fitness may attenuate the changes in central arterial stiffness and blood pressure that are associated with the FABP2 genotype.

scholarly journals Kidney transplantation and bone disease: risk factors of development and diagnostics

2017 ◽  
Vol 19 (1) ◽  
pp. 111-121
Author(s):  
O. N. Vetchinnikova
Keyword(s):  
Risk Factors ◽  
Kidney Transplantation ◽  
Bone Disease ◽  
Disease Risk ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Diagnostic Algorithm ◽  
Dynamic Monitoring ◽  
Bone Disorders ◽  
Osteoporosis Risk Factors

Bone disease is a serious and common condition in patients after kidney transplantation. The review analyzed the causes of bone disorders in the early and late postoperative period that are associated with renal transplantation: fibroblast growth factor 23, parathyroid hormone, vitamin D, immunosuppressive therapy and imbalance of mineral metabolism. It shows the most common clinical variant of the post-transplant bone disease – secondary osteoporosis, risk factors of its development and complications. It presents the diagnostic algorithm for dynamic monitoring and evaluating the effectiveness of the treatment of bone disorders

scholarly journals Exposure to Particulate Matter Is Associated With Elevated Blood Pressure and Incident Hypertension in Urban India

Hypertension ◽  
2020 ◽  
Vol 76 (4) ◽  
pp. 1289-1298 ◽  
Author(s):  
Dorairaj Prabhakaran ◽  
Siddhartha Mandal ◽  
Bhargav Krishna ◽  
Melina Magsumbol ◽  
Kalpana Singh ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Air Pollution ◽  
Particulate Matter ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Ambient Air ◽  
Interquartile Range ◽  
Ambient Air Pollution ◽  
Incident Hypertension

Ambient air pollution, specifically particulate matter of diameter <2.5 μm, is reportedly associated with cardiovascular disease risk. However, evidence linking particulate matter of diameter <2.5 μm and blood pressure (BP) is largely from cross-sectional studies and from settings with lower concentrations of particulate matter of diameter <2.5 μm, with exposures not accounting for myriad time-varying and other factors such as built environment. This study aimed to study the association between long- and short-term ambient particulate matter of diameter <2.5 μm exposure from a hybrid spatiotemporal model at 1-km×1-km spatial resolution with longitudinally measured systolic and diastolic BP and incident hypertension in 5342 participants from urban Delhi, India, within an ongoing representative urban adult cohort study. Median annual and monthly exposure at baseline was 92.1 μg/m 3 (interquartile range, 87.6–95.7) and 82.4 μg/m 3 (interquartile range, 68.4–107.0), respectively. We observed higher average systolic BP (1.77 mm Hg [95% CI, 0.97–2.56] and 3.33 mm Hg [95% CI, 1.12–5.52]) per interquartile range differences in monthly and annual exposures, respectively, after adjusting for covariates. Additionally, interquartile range differences in long-term exposures of 1, 1.5, and 2 years increased the risk of incident hypertension by 1.53× (95% CI, 1.19–1.96), 1.59× (95% CI, 1.31–1.92), and 1.16× (95% CI, 0.95–1.43), respectively. Observed effects were larger in individuals with higher waist-hip ratios. Our data strongly support a temporal association between high levels of ambient air pollution, higher systolic BP, and incident hypertension. Given that high BP is an important risk factor of cardiovascular disease, reducing ambient air pollution is likely to have meaningful clinical and public health benefits.

scholarly journals Gla-Rich Protein (GRP) as an Early and Novel Marker of Vascular Calcification and Kidney Dysfunction in Diabetic Patients with CKD: A Pilot Cross-Sectional Study

2020 ◽  
Vol 9 (3) ◽  
pp. 635 ◽  
Author(s):  
Ana P. Silva ◽  
Carla S.B. Viegas ◽  
Filipa Mendes ◽  
Ana Macedo ◽  
Patrícia Guilherme ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Positive Association ◽  
Serum Levels ◽  
Diabetic Patients ◽  
Mineral And Bone Disorder ◽  
Cross Sectional ◽  
Low Levels ◽  
Fgf 23

Vascular calcification (VC) is one of the strongest predictors of cardiovascular risk in chronic kidney disease (CKD) patients. New diagnostic/prognostic tools are required for early detection of VC allowing interventional strategies. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor, whose clinical utility is here highlighted. The present study explores, for the first time, correlations between levels of GRP in serum with CKD developmental stage, mineral metabolism markers, VC and pulse pressure (PP), in a cohort of 80 diabetic patients with mild to moderate CKD (stages 2–4). Spearman’s correlation analysis revealed a positive association of GRP serum levels with estimated glomerular filtration rate (eGFR) and α-Klotho, while a negative correlation with phosphate (P), fibroblast growth factor 23 (FGF-23), vascular calcification score (VCS), PP, calcium (x) phosphate (CaxP) and interleukin 6 (IL-6). Serum GRP levels were found to progressively decrease from stage 2 to stage 4 CKD. Multivariate analysis identified low levels of eGFR and GRP, and high levels of FGF-23 associated with both the VCS and PP. These results indicate an association between GRP, renal dysfunction and CKD-mineral and bone disorder. The relationship between low levels of GRP and vascular calcifications suggests a future, potential utility for GRP as an early marker of vascular damage in CKD.

Bone and Mineral Metabolism in Children with Nephropathic Cystinosis Compared with other CKD Entities

2020 ◽  
Vol 105 (8) ◽  
pp. e2738-e2752 ◽  
Author(s):  
Annika Ewert ◽  
Maren Leifheit-Nestler ◽  
Katharina Hohenfellner ◽  
Anja Büscher ◽  
Markus J Kemper ◽  
...  
Keyword(s):  
Biochemical Parameters ◽  
Fanconi Syndrome ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Bone Alkaline Phosphatase ◽  
Tartrate Resistant Acid Phosphatase ◽  
Nephropathic Cystinosis ◽  
Cross Sectional ◽  
Increased Risk ◽  
Ckd Stage

Abstract Context Children with nephropathic cystinosis (NC) show persistent hypophosphatemia, due to Fanconi syndrome, as well as mineral and bone disorders related to chronic kidney disease (CKD); however, systematic analyses are lacking. Objective To compare biochemical parameters of bone and mineral metabolism between children with NC and controls across all stages of CKD. Design Cross-sectional multicenter study. Setting Hospital clinics. Patients Forty-nine children with NC, 80 CKD controls of the same age and CKD stage. Main outcome measures Fibroblast growth factor 23 (FGF23), soluble Klotho, bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin, osteoprotegerin (OPG), biochemical parameters related to mineral metabolism, and skeletal comorbidity. Results Despite Fanconi syndrome medication, NC patients showed an 11-fold increased risk of short stature, bone deformities, and/or requirement for skeletal surgery compared with CKD controls. This was associated with a higher frequency of risk factors such as hypophosphatemia, hypocalcemia, low parathyroid hormone (PTH), metabolic acidosis, and a specific CKD stage-dependent pattern of bone marker alterations. Pretransplant NC patients in mild to moderate CKD showed a delayed increase or lacked an increase in FGF23 and sclerostin, and increased BAP, TRAP5b, and OPG concentrations compared with CKD controls. Post-transplant, BAP and OPG returned to normal, TRAP5b further increased, whereas FGF23 and PTH were less elevated compared with CKD controls and associated with higher serum phosphate. Conclusions Patients with NC show more severe skeletal comorbidity associated with distinct CKD stage-dependent alterations of bone metabolism than CKD controls, suggesting impaired mineralization and increased bone resorption, which is only partially normalized after renal transplantation.

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