David A Drew1, Ronit Katz2, Stephen Kritchevsky3, Joachim H Ix4, Michael G Shlipak5,6, Anne B Newman6, Andrew N Hoofnagle2, Linda F Fried7,8,9, Mark Sarnak10, Orlando M Gutiérrez11, Richard D Semba12, Javier A Neyra13,14,15. 1. Division of Nephrology, Tufts Medical Center, Boston, Massachusetts ddrew@tuftsmedicalcenter.org javier.neyra@uky.edu. 2. Kidney Research Institute, University of Washington, Seattle, Washington. 3. Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina. 4. Division of Nephrology-Hypertension, University of California San Diego School of Medicine, San Diego, California. 5. Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System, San Francisco, California. 6. Kidney Health Research Collaborative, University of California San Francisco, San Francisco, California. 7. University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania. 8. Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania. 9. University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. 10. Division of Nephrology, Tufts Medical Center, Boston, Massachusetts. 11. Medicine - Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama. 12. Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, Maryland. 13. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas ddrew@tuftsmedicalcenter.org javier.neyra@uky.edu. 14. The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, Dallas, Texas. 15. Division of Nephrology, University of Kentucky Medical Center, Lexington, Kentucky.
Abstract
BACKGROUND AND OBJECTIVES: Hypertension 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, & MEASUREMENTS: Within 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. RESULTS: The 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). CONCLUSIONS: Higher klotho is associated with higher baseline diastolic but not systolic BP, a lower risk of incident hypertension, and lower BP trajectories during follow-up.
BACKGROUND AND OBJECTIVES: Hypertension 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, & MEASUREMENTS: Within 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. RESULTS: The 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). CONCLUSIONS: Higher klotho is associated with higher baseline diastolic but not systolic BP, a lower risk of incident hypertension, and lower BP trajectories during follow-up.
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