Serum active 1,25(OH)2D, but not inactive 25(OH)D vitamin D levels are associated with cardiometabolic and cardiovascular disease risk in psoriasis


      • Serum 1,25(OH)2D but not 25(OH)D levels are inversely associated with psoriasis disease severity.
      • Serum 1,25(OH)2D but not 25(OH)D levels are inversely associated with surrogate markers of cardiovascular risk in psoriasis.
      • Serum 1,25(OH)2D but not 25(OH)D levels are inversely associated with visceral adiposity in psoriasis.
      • Serum 1,25(OH)2D but not 25(OH)D levels increase with psoriasis disease improvement.


      Background and aims

      Vitamin D exists as an inactive 25-hydroxyvitamin D (25(OH)D) in the bloodstream, which is converted to active 1,25-dihydroxyvitaminD (1,25(OH)2D) in target tissues. Cohort studies reporting cardiovascular disease among individuals with low vitamin D are inconsistent and solely measure 25(OH)D. Psoriasis, a chronic inflammatory disease, is a vitamin D deficient state and is associated with increased cardiovascular disease risk. While serum 25(OH)D is routinely measured, we hypothesized that measurement of 1,25(OH)2D in psoriasis may perform better than 25(OH)D in capturing cardiovascular risk.


      Consecutive psoriasis patients (N = 122) at baseline underwent FDG PET/CT and CCTA scans to measure visceral adipose volume, aortic vascular uptake of FDG, and coronary plaque burden respectively. Blood levels of both 1,25(OH)2D and 25(OH)D were measured by chemiluminescence (LIAISON XL DIaSorin, Stillwater, MN).


      The psoriasis cohort was middle-aged (mean ± SD: 49.6 ± 13.0), predominantly male (n = 71, 58%), in majority Caucasians (n = 98, 80%), and had moderate-to-severe skin disease [psoriasis area severity index score, PASI score, med. (IQR): 5.5 (3.2–10.7)], with almost one-fourth of the cohort on biologic psoriasis therapy for skin disease management (n = 32, 27%) at baseline. Interestingly, serum levels of 1,25(OH)2D but not 25(OH)D were found to be inversely associated with visceral adipose, a marker of cardiometabolic risk in fully adjusted models (β = − 0.43, p = 0.026 and β = −0.26 p = 0.13). Similarly, we found an inverse relationship between 1,25(OH)2D, but not 25(OH)D, and aortic vascular uptake of FDG independent of traditional risk factors (β = −0.19, p = 0.01). Finally, we found that serum 1,25(OH)2D, but not 25(OH)D, was inversely associated with non-calcified coronary plaque burden, as measured by CCTA independent of traditional risk factors (β = −0.18, p = 0.03).


      In conclusion, we demonstrate that low 1,25(OH)2D levels were associated with visceral adipose volume, vascular uptake of FDG and coronary plaque burden independent of traditional risk factors, suggesting that 1,25(OH)2D may better capture the cardiometabolic risk associated with vitamin D deficient states.

      Graphical abstract


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Jones G.
        The discovery and synthesis of the nutritional factor vitamin D.
        Int. J. Paleopathol. 2018; 23: 96-99
        • Pike J.W.
        • Christakos S.
        Biology and mechanisms of action of the vitamin D hormone.
        Endocrinol Metab. Clin. N. Am. 2017; 46: 815-843
        • Renkema K.Y.
        • Alexander R.T.
        • Bindels R.J.
        • et al.
        Calcium and phosphate homeostasis: concerted interplay of new regulators.
        Ann. Med. 2008; 40: 82-91
        • Dadaei T.
        • Safapoor M.H.
        • Asadzadeh Aghdaei H.
        • et al.
        Effect of vitamin D3 supplementation on TNF-alpha serum level and disease activity index in Iranian IBD patients.
        Gastroenterol. hepatol. Bed. Bench. 2015; 8: 49-55
        • Hong Q.
        • Xu J.
        • Xu S.
        • et al.
        Associations between serum 25-hydroxyvitamin D and disease activity, inflammatory cytokines and bone loss in patients with rheumatoid arthritis.
        Rheumatology. 2014; 53: 1994-2001
        • Sotirchos E.S.
        • Bhargava P.
        • Eckstein C.
        • et al.
        Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis.
        Neurology. 2016; 86: 382-390
        • Nardin M.
        • Verdoia M.
        • Schaffer A.
        • et al.
        Vitamin D status, diabetes mellitus and coronary artery disease in patients undergoing coronary angiography.
        Atherosclerosis. 2016; 250: 114-121
        • Deluca H.F.
        History of the discovery of vitamin D and its active metabolites.
        BoneKEy Rep. 2014; 3: 479
        • Kuehl B.
        • Shear N.H.
        The evolution of topical formulations in psoriasis.
        Skin therapy lett. 2018; 23: 5-9
        • Gelfand J.M.
        • Dommasch E.D.
        • Shin D.B.
        • et al.
        The risk of stroke in patients with psoriasis.
        J. Investig. Dermatol. 2009; 129: 2411-2418
        • Gelfand J.M.
        • Neimann A.L.
        • Shin D.B.
        • et al.
        Risk of myocardial infarction in patients with psoriasis.
        Jama. 2006; 296: 1735-1741
        • Ahlehoff O.
        • Gislason G.H.
        • Lindhardsen J.
        • et al.
        Prognosis following first-time myocardial infarction in patients with psoriasis: a Danish nationwide cohort study.
        J. Intern. Med. 2011; 270: 237-244
        • Lerman J.B.
        • Joshi A.A.
        • Chaturvedi A.
        • et al.
        Coronary plaque characterization in psoriasis reveals high-risk features that improve after treatment in a prospective observational study.
        Circulation. 2017; 136: 263-276
        • Naik H.B.
        • Natarajan B.
        • Stansky E.
        • et al.
        Severity of psoriasis associates with aortic vascular inflammation detected by FDG PET/CT and neutrophil activation in a prospective observational study.
        Arterioscler. Thromb. Vasc. Biol. 2015; 35: 2667-2676
        • Harrington C.L.
        • Dey A.K.
        • Yunus R.
        • et al.
        Psoriasis as a human model of disease to study inflammatory atherogenesis.
        Am. J. Physiol. Heart Circ. Physiol. 2017; 312: H867-h873
        • Dey A.K.
        • Joshi A.A.
        • Chaturvedi A.
        • et al.
        Association between skin and aortic vascular inflammation in patients with psoriasis: a case-cohort study using Positron emission tomography/computed tomography.
        JAMA Cardiol. 2017; 2: 1013-1018
        • Manson J.E.
        • Cook N.R.
        • Lee I.M.
        • et al.
        Vitamin D supplements and prevention of cancer and cardiovascular disease.
        N. Engl. J. Med. 2019; 380: 33-44
        • Zhang R.
        • Li B.
        • Gao X.
        • et al.
        Serum 25-hydroxyvitamin D and the risk of cardiovascular disease: dose-response meta-analysis of prospective studies.
        Am. J. Clin. Nutr. 2017; 105: 810-819
        • Tunon J.
        • Cristobal C.
        • Tarin N.
        • et al.
        Coexistence of low vitamin D and high fibroblast growth factor-23 plasma levels predicts an adverse outcome in patients with coronary artery disease.
        PLoS One. 2014; 9e95402
        • Joshi A.A.
        • Lerman J.B.
        • Dey A.K.
        • et al.
        Association between aortic vascular inflammation and coronary artery plaque characteristics in psoriasis.
        JAMA Cardiol. 2018; 3: 949-956
        • Gruson D.
        • Ferracin B.
        • Ahn S.A.
        • et al.
        1,25-Dihydroxyvitamin D to PTH(1-84) ratios strongly predict cardiovascular death in heart failure.
        PLoS One. 2015; 10e0135427
        • Valcour A.
        • Zierold C.
        • Podgorski A.L.
        • et al.
        A novel, fully-automated, chemiluminescent assay for the detection of 1,25-dihydroxyvitamin D in biological samples.
        J. Steroid Biochem. Mol. Biol. 2016; 164: 120-126
        • Salahuddin T.
        • Natarajan B.
        • Playford M.P.
        • et al.
        Cholesterol efflux capacity in humans with psoriasis is inversely related to non-calcified burden of coronary atherosclerosis.
        Eur. Heart J. 2015; 36: 2662-2665
        • Pludowski P.
        • Holick M.F.
        • Grant W.B.
        • et al.
        Vitamin D supplementation guidelines.
        J. Steroid Biochem. Mol. Biol. 2018; 175: 125-135
        • Fleming P.
        • Kraft J.
        • Gulliver W.P.
        • et al.
        The relationship of obesity with the severity of psoriasis: a systematic review.
        J. Cutan. Med. Surg. 2015; 19: 450-456
        • Rivers J.P.
        • Powell-Wiley T.M.
        • Dey A.K.
        • et al.
        Visceral adiposity in psoriasis is associated with vascular inflammation by (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography beyond cardiometabolic disease risk factors in an observational cohort study.
        JACC. JACC. Cardiovas. imaging. 2018; 11: 349-357
        • Matsuzawa Y.
        The role of fat topology in the risk of disease.
        Int. J. Obes. 2008; 32 (2005): S83-S92
        • Naik H.B.
        • Natarajan B.
        • Stansky E.
        • et al.
        Severity of psoriasis associates with aortic vascular inflammation detected by FDG PET/CT and neutrophil activation in a prospective observational study.
        Arterioscler. Thromb. Vasc. Biol. 2015; 35: 2667-2676
        • Santos-Gallego C.G.
        • Picatoste B.
        • Badimon J.J.
        Pathophysiology of acute coronary syndrome.
        Curr. Atheroscler. Rep. 2014; 16: 401
        • Raggi P.
        • Genest J.
        • Giles J.T.
        • et al.
        Role of inflammation in the pathogenesis of atherosclerosis and therapeutic interventions.
        Atherosclerosis. 2018; 276: 98-108
        • Mehta N.N.
        • Shin D.B.
        • Joshi A.A.
        • et al.
        Effect of 2 psoriasis treatments on vascular inflammation and novel inflammatory cardiovascular biomarkers: a randomized placebo-controlled trial, circulation.
        JACC. Cardiovas. imaging. 2018; 11e007394
        • Pilz S.
        • Verheyen N.
        • Grubler M.R.
        • et al.
        Vitamin D and cardiovascular disease prevention.
        Nat. Rev. Cardiol. 2016; 13: 404-417
        • Scragg R.
        • Stewart A.W.
        • Waayer D.
        • et al.
        Effect of monthly high-dose vitamin D supplementation on cardiovascular disease in the vitamin D assessment study : a randomized clinical trial.
        JAMA Cardiol. 2017; 2: 608-616
        • Norman P.E.
        • Powell J.T.
        Vitamin D and cardiovascular disease.
        Circ. Res. 2014; 114: 379-393
        • Kudo K.
        • Hasegawa S.
        • Suzuki Y.
        • et al.
        1alpha,25-Dihydroxyvitamin D(3) inhibits vascular cellular adhesion molecule-1 expression and interleukin-8 production in human coronary arterial endothelial cells.
        J. Steroid Biochem. Mol. Biol. 2012; 132: 290-294
        • Stach K.
        • Kalsch A.I.
        • Nguyen X.D.
        • et al.
        1alpha,25-dihydroxyvitamin D3 attenuates platelet activation and the expression of VCAM-1 and MT1-MMP in human endothelial cells.
        Cardiology. 2011; 118: 107-115
        • Won S.
        • Sayeed I.
        • Peterson B.L.
        • et al.
        Vitamin D prevents hypoxia/reoxygenation-induced blood-brain barrier disruption via vitamin D receptor-mediated NF-kB signaling pathways.
        PLoS One. 2015; 10e0122821
        • Oh J.
        • Weng S.
        • Felton S.K.
        • et al.
        1,25(OH)2 vitamin d inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus.
        Circulation. 2009; 120: 687-698
        • Yin K.
        • You Y.
        • Swier V.
        • et al.
        Vitamin D protects against atherosclerosis via regulation of cholesterol efflux and macrophage polarization in hypercholesterolemic swine.
        Arterioscler. Thromb. Vasc. Biol. 2015; 35: 2432-2442
        • Zhong W.
        • Gu B.
        • Gu Y.
        • et al.
        Activation of vitamin D receptor promotes VEGF and CuZn- SOD expression in endothelial cells.
        J. Steroid Biochem. Mol. Biol. 2014; 140: 56-62
        • Absi M.
        • Ward D.T.
        Increased endothelin-1 responsiveness in human coronary artery smooth muscle cells exposed to 1,25-dihydroxyvitamin D(3).
        Am. J. Physiol. Cell Physiol. 2013; 304: C666-C672
        • Baumer Y.
        • Ng Q.
        • Sanda G.E.
        • et al.
        Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis.
        JCI insight. 2018; 3
        • Christakos S.
        • Dhawan P.
        • Verstuyf A.
        • et al.
        Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects.
        Physiol. Rev. 2016; 96: 365-408
        • Pascoe V.L.
        • Kimball A.B.
        Seasonal variation of acne and psoriasis: a 3-year study using the Physician Global Assessment severity scale.
        J. Am. Acad. Dermatol. 2015; 73: 523-525