Prof.dr. Sekib Sokolovic,EHS, F.E.S.C. University Clinical Center Sarajevo and Medical Faculty

1. Meeting of the Balkan Excellent Centers “Vitamin D and Arterial Stiffnes” Prof.dr. Sekib Sokolovic,EHS, F.E.S.C. University Clinical Center Sarajevo and Medical Faculty Cardiology Clinic Postintensive and Postsurgery Cardiology Care Department Sarajevo, Bosnia and Herzegovina

2. Abstract The correlation between the arterial stiffness and Vitamin D has been examined in a certain studies. Measurement of the arterial stiffness has been recommended in a new ESC/ESH guidelines for the arterial hypertension. In order to evaluate arterial stiffness, the measurement of aortic pulse wave velocity, (APWV) and Augmentation Index (AI) was performed using AgedioArteriograph. The estimation of cardiovascular risk factors was performed in all 88 subjects and two group were formed. Vitamin D has been evaluated in a hypertensive and normotensive patients. The open outpatient controlled prospective study has been designed. Preliminary results showed the significant increase in PWV with average values of 10, 1 m/sec in hypertensive patients compared to 7, 7 m/sec in normotensive ones. The Augmentation index was borderline at 32, 75%, ranging from 24-56% vs 27, 25%. Average blood pressure was 172/109,5mmHg, compared to 128/82 mmHg and heart rate was 70b/min in average vs. 89,5b/m. Vitamin D average level in hypertensives was 16,9ng/ml compared to 28,0 ng/ml in normotensive ones. The arterial stiffness has been provedsignificant in hypertensive patients with vitamin D deficiency.

3. NORMAL DEFICINECY Vitamin D deficit–EUROPEAN PROBLEM of PUBLIC HEALTH

4. RAS and VIT D • Decreased renin and angiotensin II levels were observed in several, but not all, studies that examined the activity of the RAAS after treatment with vitamin D, 1,25(OH)2D or active vitamin D analogs • Sugden, J. A., et al,Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels. Diabet. Med. 25, 320-325 (2008). • Park, C. W. et al. Intravenous calcitriol regresses myocardial hypertrophy in hemodialysis patients with secondary hyperparathyroidism. Am. J.Kidney Dis. 33, 73-81 (1999). • Lind, L., et al, Reduction of blood pressure during long-term treatment with active vitamin D (alphacalcidol) is dependent on plasma renin activity and calcium status. A double-blind, placebo-controlled study. Am. J. Hypertens. 2, 20-25 (1989). • Kimura, Y. et al. Effectiveness of 1,25-dihydroxyvitamin D supplementation on blood pressure reduction in a pseudohypoparathyroidism patient with high renin activity.Intern. Med. 38, 31-35 (1999). • Resnick, L. M. et al. Does 1,25 dihydroxyvitamin D (1.25D) cause low renin hypertension? [abstract] Hypertension 6, 792 (1984). • Freundlich, M. et al. Suppression of renin-angiotensin gene expression in the kidney by paracalcitol. Kidney Int. 74, 1394-1402 (2008).

6. Antihypertensive effects of vit D • Suppression of Renin and PTH • Renoprotective, anti-inflammatory and vasculoprotective properties • Low Vit D : Independent risk factor for incident HTA • Pilz S1, Tomaschitz A. Expert Rev Cardiovasc Ther. 2010 Nov;8(11):1599-608. doi: 10.1586/erc.10.142.

7. Arterial Stiffness and Vitamin D Levels: the Baltimore Longitudinal Study of Aging • Francesco Giallauria et al,  2012 • To test that 25-hydroxyvitamin D (25-OH D) is an independent cross-sectional correlate of central arterial stiffness in a normative aging • Vit D levels are inversely associated with increased arterial stiffness irrespective of traditional risk factor burden 

8. Diabetes Care 2015 • Pranati Jha, et al: Low Serum Vitamin D Levels Are Associated With Increased Arterial Stiffness in Youth With Type 2 Diabetes • 25[OH]D is inversely associated with arterial stiffness in lean adolescents and obese adolescents with T2DM but not in obese normoglycemic adolescents •  The mean 25[OH]D levels were 21.27, 14.29, and 14.13 ng/mL in lean individuals, obese individuals, and obese individuals with T2DM(P < 0.01) • 3 ng/mL ↑in 25[OH]D was associated with Aix of 1%

9. Diabetes Res Clin Pract. 2012 • Serum 25-hydroxyvitamin D concentration and arterial stiffness among type 2 diabetes • Lee JI1, et al, • Prevalence of vit D deficiency: 85.9%. • Lower vitamin D...more increased PWV  • Vitamin D deficiency is common in type 2 diabetes, and significantly associated with increased arterial stiffness in DM

10. PILOT STUDY Vit.n D status of adults: Bosnia >30 ng/mL <20 ng/mL 20-30 ng/mL

11. Average value of serum 25(OH)D • Minimal value 3.0 ng/mL • Maximum of 70.0 ng/mL. • Median vitamin D level: 16.9 ng/mL • Interquartile range 9.6-26.2 ng/mL (Kolmogorov-Smirnovtest) p=0,000) • Severe VD deff (<10 ng/mL): 25.9% • Deff of VD (10-20 ng/mL): 34.7% • Insuff. of VD (20-30 ng/mL) 21.4% • Sufficient VitD >30ng/ml 18.0%

12. 3-D ECHO

13. Preliminary results HYPERTENSIVE PTS: 88pts with decreased VIT D: Significant increase in PWV : Average of 10,1 m/sec Augmentation index: borderline:32,75%,(24-56%) Average BP:172/109,5mmHg, HR70b/min NORMOTENSIVE PTS: Average: PWV:7,75 m/sec, Augmentation Index: Average of 27,25%. Average BP: 128/82,75mmHg,HR 89,5b/min.

14. VITAMIN D/Ca score/Arterial Stiffness: Case report • Female 65 y/old • Vitamin D: 28 • Calcium score: LAD: 17, Cx: 19 • LAD: Stenosis less than 50% • PWV: 8,5 m/sec • Augm. Index: 20% • SV: 3,8L/min • RR: 102/81, puls 88/min • Vascular age: 3 years younger

15. CONCLUSION • The arterial stiffness has been proved significant in hypertensive patients with defficient vitamin D level