title: Urinary Potassium Excretion and Risk of Developing Hypertension: The Prevention of Renal and Vascular End-Stage Disease Study Association between circulating 25-hydroxyvitamin D and incident type 2 diabetes: a mendelian randomisation study Plasma 1,25-Dihydroxyvitamin D and the Risk of Developing Hypertension: The Prevention of Renal and Vascular End-Stage Disease Study
abstract: Previous prospect i ve cohort studies on the association between potassium intake and risk of hypertension have almost exclusively relied on self-reported dietary data , whereas repeated 24-hour urine excretions , as estimate of dietary uptake , may provide a more objective and quantitative estimate of this association . Risk of hypertension ( defined as blood pressure ≥140/90 mm Hg or initiation of blood pressure – lowering drugs ) was prospect ively studied in 5511 normotensive subjects aged 28 to 75 years not using blood pressure – lowering drugs at baseline of the Prevention of Renal and Vascular End-Stage Disease ( PREVEND ) study . Potassium excretion was measured in two 24-hour urine specimens at baseline ( 1997–1998 ) and midway during follow-up ( 2001–2003 ) . Baseline median potassium excretion was 70 mmol/24 h ( interquartile range , 57–85 mmol/24 h ) , which corresponds to a dietary potassium intake of ≈91 mmol/24 h. During a median follow-up of 7.6 years ( interquartile range , 5.0–9.3 years ) , 1172 subjects developed hypertension . The lowest sex-specific tertile of potassium excretion ( men : < 68 mmol/24 h ; women : < 58 mmol/24 h ) had an increased risk of hypertension after multivariable adjustment ( hazard ratio , 1.20 ; 95 % confidence interval , 1.05–1.37 ) , compared with the upper 2 tertiles ( Pnonlinearity=0.008 ) . The proportion of hypertension attributable to low potassium excretion was 6.2 % ( 95 % confidence interval , 1.7%–10.9 % ) . No association was found between the sodium to potassium excretion ratio and risk of hypertension after multivariable adjustment . Low urinary potassium excretion was associated with an increased risk of developing hypertension  . Dietary strategies to increase potassium intake to the recommended level of 90 mmol/d may have the potential to reduce the incidence of hypertension Summary Background Low circulating concentrations of 25-hydroxyvitamin D ( 25[OH]D ) , a marker of vitamin D status , are associated with an increased risk of type 2 diabetes  , but whether this association is causal remains unclear . We aim ed to estimate the unconfounded , causal association between 25(OH)D concentration and risk of type 2 diabetes using a mendelian r and omisation approach . Methods Using several data sources from population s of European descent , including type 2 diabetes cases and non-cases , we did a mendelian r and omisation analysis using single nucleotide polymorphisms ( SNPs ) within or near four genes related to 25(OH)D synthesis and metabolism : DHCR7 ( related to vitamin D synthesis ) , CYP2R1 ( hepatic 25-hydroxylation ) , DBP ( also known as GC ; transport ) , and CYP24A1 ( catabolism ) . We assessed each SNP for an association  with circulating 25(OH)D concentration ( 5449 non-cases ; two studies ) , risk of type 2 diabetes ( 28 144 cases , 76 344 non-cases ; five studies ) , and glycaemic traits ( concentrations of fasting glucose , 2-h glucose , fasting insulin , and HbA1c  ; 46 368 non-cases ; study consortium ) . We combined these associations in a likelihood-based mendelian r and omisation analysis to estimate the causal association of 25(OH)D concentration with type 2 diabetes and the glycaemic traits , and compared them with that from a meta- analysis of data from observational studies ( 8492 cases , 89 698 non-cases ; 22 studies ) that assessed the association between 25(OH)D concentration and type 2 diabetes . Findings All four SNPs were associated with 25(OH)D concentrations ( p<10−6 ) . The mendelian r and omisation-derived unconfounded odds ratio for type 2 diabetes was 1·01 ( 95 % CI 0·75–1·36 ; p=0·94 ) per 25·0 nmol/L ( 1 SD ) lower 25(OH)D concentration . The corresponding ( potentially confounded ) relative risk from the meta- analysis of data from observational studies was 1·21 ( 1·16–1·27 ; p=7·3 × 10−19 ) . The mendelian r and omisation-derived estimates for glycaemic traits were not significant ( p>0·25 ) . Interpretation The association between 25(OH)D concentration and type 2 diabetes is unlikely to be causal . Efforts to increase 25(OH)D concentrations might not reduce the risk of type 2 diabetes as would be expected on the basis of observational evidence . These findings warrant further investigations to identify causal factors that might increase 25(OH)D concentration and also reduce the risk of type 2 diabetes . Funding UK Medical Research Council Epidemiology Unit and European Union Sixth Framework Programme 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 prospect ively 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-t and em 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
target: CONCLUSION Our meta- analysis highlights that hypovitaminosis D is associated with orthostatic hypotension , independent of potential confounders .
background: OBJECTIVES Orthostatic hypotension is a common condition among older adults and is associated with a range of deleterious outcomes .
  Recently , interest has developed in hypovitaminosis D ( defined as low 25 hydroxiyvitamin D levels ) as a potential risk factor for orthostatic hypotension .
  We conducted a systematic review and meta- analysis examining the association of orthostatic hypotension between study participants with and without hypovitaminosis D , including the adjustment of potential confounders ( age , sex , BMI , renal function , comorbidities , seasonality , use of antihypertensive medications , and supplementation with cholecalciferol ) .