Vitamin D and Cardiometabolic risk

Transcription

1 Vitamin D and Cardiometabolic risk 서울의대, 분당서울대병원 내과 최 성 희 2013년 대한당뇨병학회 춘계학술대회

2 Metabolism Of Vitamin D

3 Risk factors for vitamin D deficiency - Aging decreased concentrations of 7-dehydro-cholesterol in the skin - Obesity is associated with sequestration of vitamin D - Darker skin is associated with decreased absorbance of UVB light - Institutionalized or homebound - Increased distance from equator - Cover up clothing and/or sunscreen - Renal disease, liver disease - Medications Antiseizure - need 2X or 3X more to compensate Prednisone AIDS drugs St Johns wort Orlistat (for obesity) need 3000 to 4000 IU Questran (lower cholesterol) wait 2-4 hours after taking the medicine before taking vitamin D S. Makariou et al. / European Journal of Internal Medicine 22 (2011)

4 Vitamin D deficiency Cut-points for serum 25(OH) Vit D levels in adults 30 ng/ml : vitamin D sufficiency ng/ml : insufficiency 20 ng/ml : deficiency S. Makariou et al. / European Journal of Internal Medicine 22 (2011)

5 Endocrine, paracrine and intracrine functions of Vitamin D BP & Systemic Inflammation 의 증가 : Atherosclerosis & CVD 연관성

6 Proposed pleiotropic effects of vitamin D RAS 억제 인슐린생성/분비촉진 V.M. Brandenburg et al. / Atherosclerosis 225 (2012)

7 The intricate relationship between the effects of vitamin D, calcium, and 9-cis-retinoic acid on tissues of the colorectum. Jacobs E T et al. Cancer Epidemiol Biomarkers Prev 2005;14: by American Association for Cancer Research

8 Vitamin D : New roles in Cardiometabolic risk Vitamin D and cardiovascular disease 1) Previous studies 2) Proposed protective mechanism 3) randomized controlled trials

9 A correlation between vitamin D and CV disease Several observations in the early 1980s and 1990s sugge sted that vitamin D could explain differences in mortality from ischemic heart disease Vitamin D? Camargo.Jr et al. / Journal of the American College of Cardiology 58(14) (2011)

10 Metabolic Syndrome After adjustments for known risk factors, odd of metabolic syndrome decreased progressively across increasing concentrations of 25(OH)D Relative risk compared with bottom quintile of vitamin D level: 2 nd quintile rd quintile th quintile th quintile 0.46 Ford, et al., 2005

11 A correlation between vitamin D and CV disease The National Health and Nutritional Examination Surveys (NHANES) ( , ) Framingham Offspring Study with HTN without HTN Lee et al. / Journal of the American College of Cardiology 52(24) (2008)

12 25(OH)D and Risk of Myocardial Infarction in Men : Health Professionals Follow-up Study (HPFS) Prospective study : A nested case control st udy 25(OH)D concentration & risk of CHD 18,225 men in the Health Professionals Foll ow-up Study Men aged 40 to 75 years, no CHD During 10 years of follow-up, 454 men deve loped nonfatal myocardial infarction or fatal coronary heart disease. Giovannucci et al. / Arch Intern Med. 2008;168(11):

13 25(OH)D and Risk of Myocardial Infarction in Men : Health Professionals Follow-up Study (HPFS) Estimated RRs of MI by level of 25(OH)D at baseline during 10 years of Follow-up Giovannucci et al. / Arch Intern Med. 2008;168(11):

14 Serum Vit D level & coronary artery stenosis/ccs in KLOSHA Lim S,,Choi SH, Jang HC et al. JCEM 2012

15 From: Vitamin D and Cardiovascular Disease: Will It Live Up to its Hype? J Am Coll Cardiol. 2011;58(15): doi: /j.jacc Figure Legend: Vitamin D and All-Cause and CV Mortality Kaplan-Meier plots of (A) all-cause and (B) cardiovascular (CV) mortality in the 25-hydroxyvitamin D quartiles (Q): Q1 (blue lines), Q2 (green lines), Q3 (orange lines), and Q4 (red lines). Log-rank test indicated a significant difference across all 25-hydroxyvitamin D quartiles (p < 0.001). This analysis was performed on 3,258 consecutive coronary angiographic patients. Date of download: 5/9/2013 Copyright The American College of Cardiology. All rights reserved.

16 Proposed protective mechanism for vitamin D in CV disease Limitation : mainly in preclinical studes with very little information available from clinical trials Lee et al. / JACC (52)24 :

17 VDR activation and RAS

18 Vitamin D intake and risk of CVD in US men and women Prospective study : Observation study Vitamin D intake and risk of CHD In the Nurses Health Study ( ) and the Health Professionals Follow-Up Study ( ) 74,272 women and 44,592 men, who were free o f CVD and cancer at baseline 9886 incident cases of coronary heart disease an d stroke / a total of 2,280,324 person-years of fo llow-up Sun et al. / Am J Clin Nutr 2011;94:

19 Vitamin D intake and risk of CVD in US men and women A higher intake of vitamin D (600IU/day) is associated with a lower risk of CVD in men but not in women. Sun et al. / Am J Clin Nutr 2011;94:

20 Vitamin D supply and CV Outcomes A Systematic Review and Meta-Analysis Vitamin D and mortality or cardiovascula r risk in interventional studies 51 randomized trials from MEDLINE, EMB ASE, Web of Science, SCOPUS, PEDRro th rough August 2010 Randomized trials that enrolled adults w ho received vitamin D supplementation a nd a concurrent comparison Elamin et al. / J Clin Endocrinol Metab, July 2011, 96(7):

21 Vitamin D and Cardiovascular Outcomes : Pooled result of mortality, MI, and stroke Elamin et al. / J Clin Endocrinol Metab, July 2011, 96(7):

22 From: Vitamin D and Cardiovascular Disease: Will It Live Up to its Hype? Vitamin D Supplementation and Mortality Meta-analysis of data on all-cause mortality in 18 randomized controlled trials with vitamin D. CI = confidence interval; SRR = summary relative risk. Date of download: 5/9/2013 Copyright The American College of Cardiology. All rights reserved.

23 Vitamin D and Cardiovascular Outcomes Vitamin D supplementation did not sig nificantly affect any of the cardiovascul ar risk factors. Elamin et al. / J Clin Endocrinol Metab, July 2011, 96(7):

24 Randomized controlled trials and vitamin D supplementation Large, population-based RCTs to formally test causality in humans : Does the initiation of vitamin D supplementati on to prevent CVD? S. Makariou et al. / European Journal of Internal Medicine 22 (2011)

25 Vitamin D and insulin secretion with cycloheximide Increased insulin response to glucose with vitamin D P-M Bourlon et al / Journal of Endocrinology (1999) 160, 87 95

26 Vitamin D and insulin action : direct effect Increased insulin action with vitamin D Maestro et al. / Cell biochem funct 2002 ; 20 ;

27 Vitamin D and insulin secretion : direct effect Maestro et al. / Cell biochem funct 2002 ; 20 ;

28 Vitamin D and Glucose metabolism : indirect effect PPAR-δ activation by VDR From ChIP assays with chromatin isolated from 1,25(OH)2D3-treated MCF-7 cells Thomas et al / Journal of Mol biology (2005) 349,

29 Vit D intake and the risk of T2DM Vitamin D and Type 2 diabetes in 20% 이상 risk reduction the Nurses health study Pittas et al. / Diabetes Care 29 :650 6, 2006

30 Metabolic syndrome in adolescents in NHANES The prevalence of metabolic syndrome was higher in those with serum 25(OH)D,50 nmol/l compared with those with serum 25(OH)D 75 nmol/l (7.5% compared with 3.5%; P = 0.001). Ganji et al. / Am J Clin Nutr 2011;94:

31 Cumulative incidence of diabetes by calcium/ vitamin D treatment assignment in the women s health initiative (WHI) Were the doses used in the WHI CaD trial were insufficient to prevent diabetes? Do really calcium and vitamin D have no causal effect on glucose metabolism? de Boer et al. / Diabetes Care 31: , 2008

32 Current recommendation of vitamin D supplementation National Osteoporosis Foundation currently recommends IU of vitamin D daily for adults under 50 and IU of vitamin D daily for adults aged over 50. Supplementation of up to 2000 IU vitamin D daily has b een generally recognized as effective and safe by U.S. FD A guidelines. However, regional difference (such as young age, occupa tion in Korea) should be considered.

33 Treatment recommendation for vitamin D deficiency U SHAPED CURVE (NOT WITH STATISTICAL SIGNIFICANCE)

34 Current recommendation and future aspects of vitamin D Potential effect of vitamin D in cardiometabolic risk shoul d be further studies 1) Translational research to improve understanding of pot ential mechanisms 2) Large, population-based RCTs to formally test causality in humans.

35 Summary Journal of the American College of Cardiology 52(24) (2008)

36 Thank you for your attention.