title: Plasma 1,25-Dihydroxyvitamin D and the Risk of Developing Hypertension: The Prevention of Renal and Vascular End-Stage Disease Study.
abstract: Previous observational studies on the vascular effects of vitamin D have predominantly relied on measurement of its inactive precursor, 25-hydroxyvitamin D, whereas the active metabolite 1,25-dihydroxyvitamin D may be of more physiological relevance. We prospectively studied the associations of 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D with hypertension risk (blood pressure ≥140/90 mm Hg or initiation of blood pressure-lowering drugs) in 5066 participants aged 28 to 75 years, free of hypertension at baseline from the Prevention of Renal and Vascular End-Stage Disease Study, a well-defined cohort with serial follow-up. We measured plasma 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D using liquid chromatography-tandem mass spectrometry. Mean±SD plasma concentration of 1,25-dihydroxyvitamin D was 145±47.0 pmol/L and 25-hydroxyvitamin D was 58.6±23.8 nmol/L. During a median follow-up of 6.4 years, 1036 participants (20.5%) developed hypertension. As expected, low 25-hydroxyvitamin D was associated with a higher hypertension risk; each 1-SD decrement in 25-hydroxyvitamin D was associated with a 8% higher hypertension risk (hazard ratio, 1.08; 95% confidence interval, 1.01-1.16) after adjustment for potential confounders. However, the association of 1,25-dihydroxyvitamin D was in the opposite direction; each 1-SD decrement of 1,25-dihydroxyvitamin D was associated with a 10% lower hypertension risk (hazard ratio, 0.90; 95% confidence interval, 0.84-0.96), independent of potential confounders. In contrast to the inverse association between 25-hydroxyvitamin D and hypertension risk, 1,25-dihydroxyvitamin D was positively associated with risk of hypertension. Thus, higher circulating concentrations of 1,25-dihydroxyvitamin D are associated with a higher risk of hypertension.
authors.affiliation: From the Department of Health Sciences and the EMGO Institute, VU University, Amsterdam, The Netherlands (A.J.v.B., M.V., I.A.B.); Department of Nephrology (R.T.G., M.H.d.B., S.J.L.B., M.M.J.), Department of Clinical Pharmacy and Pharmacology (H.J.L.-H., D.d.Z.), and Department of Clinical Chemistry (I.P.K.), University Medical Center Groningen, Groningen, The Netherlands; and Top Institute Food and Nutrition, Wageningen, The Netherlands (S.J.L.B., M.M.J.).
authors.forename: Adriana J
authors.initials: AJ
authors.lastname: van Ballegooijen
authors.affiliation: From the Department of Health Sciences and the EMGO Institute, VU University, Amsterdam, The Netherlands (A.J.v.B., M.V., I.A.B.); Department of Nephrology (R.T.G., M.H.d.B., S.J.L.B., M.M.J.), Department of Clinical Pharmacy and Pharmacology (H.J.L.-H., D.d.Z.), and Department of Clinical Chemistry (I.P.K.), University Medical Center Groningen, Groningen, The Netherlands; and Top Institute Food and Nutrition, Wageningen, The Netherlands (S.J.L.B., M.M.J.).
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
authors.affiliation: From the Department of Health Sciences and the EMGO Institute, VU University, Amsterdam, The Netherlands (A.J.v.B., M.V., I.A.B.); Department of Nephrology (R.T.G., M.H.d.B., S.J.L.B., M.M.J.), Department of Clinical Pharmacy and Pharmacology (H.J.L.-H., D.d.Z.), and Department of Clinical Chemistry (I.P.K.), University Medical Center Groningen, Groningen, The Netherlands; and Top Institute Food and Nutrition, Wageningen, The Netherlands (S.J.L.B., M.M.J.).
authors.forename: Hiddo J
authors.initials: HJ
authors.lastname: Lambers-Heerspink
authors.affiliation: From the Department of Health Sciences and the EMGO Institute, VU University, Amsterdam, The Netherlands (A.J.v.B., M.V., I.A.B.); Department of Nephrology (R.T.G., M.H.d.B., S.J.L.B., M.M.J.), Department of Clinical Pharmacy and Pharmacology (H.J.L.-H., D.d.Z.), and Department of Clinical Chemistry (I.P.K.), University Medical Center Groningen, Groningen, The Netherlands; and Top Institute Food and Nutrition, Wageningen, The Netherlands (S.J.L.B., M.M.J.).
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
authors.affiliation: From the Department of Health Sciences and the EMGO Institute, VU University, Amsterdam, The Netherlands (A.J.v.B., M.V., I.A.B.); Department of Nephrology (R.T.G., M.H.d.B., S.J.L.B., M.M.J.), Department of Clinical Pharmacy and Pharmacology (H.J.L.-H., D.d.Z.), and Department of Clinical Chemistry (I.P.K.), University Medical Center Groningen, Groningen, The Netherlands; and Top Institute Food and Nutrition, Wageningen, The Netherlands (S.J.L.B., M.M.J.).
authors.forename: Marjolein
authors.initials: M
authors.lastname: Visser
authors.affiliation: From the Department of Health Sciences and the EMGO Institute, VU University, Amsterdam, The Netherlands (A.J.v.B., M.V., I.A.B.); Department of Nephrology (R.T.G., M.H.d.B., S.J.L.B., M.M.J.), Department of Clinical Pharmacy and Pharmacology (H.J.L.-H., D.d.Z.), and Department of Clinical Chemistry (I.P.K.), University Medical Center Groningen, Groningen, The Netherlands; and Top Institute Food and Nutrition, Wageningen, The Netherlands (S.J.L.B., M.M.J.).
authors.forename: Ingeborg A
authors.initials: IA
authors.lastname: Brouwer
authors.affiliation: From the Department of Health Sciences and the EMGO Institute, VU University, Amsterdam, The Netherlands (A.J.v.B., M.V., I.A.B.); Department of Nephrology (R.T.G., M.H.d.B., S.J.L.B., M.M.J.), Department of Clinical Pharmacy and Pharmacology (H.J.L.-H., D.d.Z.), and Department of Clinical Chemistry (I.P.K.), University Medical Center Groningen, Groningen, The Netherlands; and Top Institute Food and Nutrition, Wageningen, The Netherlands (S.J.L.B., M.M.J.).
authors.forename: Ido P
authors.initials: IP
authors.lastname: Kema
authors.affiliation: From the Department of Health Sciences and the EMGO Institute, VU University, Amsterdam, The Netherlands (A.J.v.B., M.V., I.A.B.); Department of Nephrology (R.T.G., M.H.d.B., S.J.L.B., M.M.J.), Department of Clinical Pharmacy and Pharmacology (H.J.L.-H., D.d.Z.), and Department of Clinical Chemistry (I.P.K.), University Medical Center Groningen, Groningen, The Netherlands; and Top Institute Food and Nutrition, Wageningen, The Netherlands (S.J.L.B., M.M.J.).
authors.forename: Martin H
authors.initials: MH
authors.lastname: de Borst
authors.affiliation: From the Department of Health Sciences and the EMGO Institute, VU University, Amsterdam, The Netherlands (A.J.v.B., M.V., I.A.B.); Department of Nephrology (R.T.G., M.H.d.B., S.J.L.B., M.M.J.), Department of Clinical Pharmacy and Pharmacology (H.J.L.-H., D.d.Z.), and Department of Clinical Chemistry (I.P.K.), University Medical Center Groningen, Groningen, The Netherlands; and Top Institute Food and Nutrition, Wageningen, The Netherlands (S.J.L.B., M.M.J.).
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: From the Department of Health Sciences and the EMGO Institute, VU University, Amsterdam, The Netherlands (A.J.v.B., M.V., I.A.B.); Department of Nephrology (R.T.G., M.H.d.B., S.J.L.B., M.M.J.), Department of Clinical Pharmacy and Pharmacology (H.J.L.-H., D.d.Z.), and Department of Clinical Chemistry (I.P.K.), University Medical Center Groningen, Groningen, The Netherlands; and Top Institute Food and Nutrition, Wageningen, The Netherlands (S.J.L.B., M.M.J.). mmjoosten@gmail.com.
authors.forename: Michel M
authors.initials: MM
authors.lastname: Joosten
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000502:physiology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000453:epidemiology*; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000097:blood / Q000453:epidemiology* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D
keywords: 1,25-dihydroxyvitamin D; 25-hydroxyvitamin D; blood pressure; hypertension; parathyroid hormone; risk factors; seasonal variation