Vitamin D Levels and Mortality in Metabolic Syndrome

10/3/2012 Gregory A. Plotnikoff, MD, MTS, FACP

In people with metabolic syndrome, vitamin D levels predict all-cause and cardiovascular mortality
Wednesday, October 03, 2012

by: Gregory A. Plotnikoff, MD, MTS, FACP Section: Abstracts & Commentary

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About the Author

Gregory A. Plotnikoff, !, "#, $ACP, is a board-certified internist and ediatrician !ho has recei"ed international honors for his !ork in crossc#lt#ral and integrati"e $edicine. %e is a grad#ate of Carleton College, %ar"ard Di"inity School, and the &ni"ersity of Minnesota Medical School. Plotnikoff is the a#thor of '( te)tbook cha ters and $ore than *+ firsta#thored articles in the $edical literat#re incl#ding se"eral in ,a anese. %is '++- article on "ita$in D and chronic ain is one of the $ost highly cited articles in the history of the Mayo Clinic Proceedings. %e is a Fello! of the &nited States-,a an Fo#ndation .eadershi rogra$, the /#sh Fo#ndation .eadershi Progra$, and the A$erican College of Physicians. Plotnikoff ser"es as an integrati"e $edicine hysician at the Penny George 0nstit#te for %ealth and %ealing and as senior cons#ltant, Center for %ealthcare 0nno"ation, Allina %ealth Care, Minnea olis, Minn. %e is also an editor of the ne! 1o#rnal Global Advances in Health and Medicine.

2eference
Tho$as G3, %artaigh /4, /osch ,A, et al. 5ita$in D le"els redict all-ca#se and cardio"asc#lar disease $ortality in s#b1ects !ith $etabolic syndro$e: The .#d!igshafen 2isk and Cardio"asc#lar health 6.&20C7 st#dy. Diabetes Care. '+('8-*:((*9-((:;.

Design
Pros ecti"e cohort st#dy of (,9+( !hite eo le in so#th!est Ger$any !ith $etabolic syndro$e !ho #nder!ent electi"e coronary angiogra hy bet!een (<<= and '+++. Mortality !as tracked for a $edian of =.= years 6(',*(; erson-years of follo!-# 7.

Methods
.e"els of '*-4%-"ita$in D !ere obtained the $orning of the angiogra hic roced#re and $eas#red by radioi$$#noassay 6DiaSorin7. Classification of death !as erfor$ed #sing re orts on death certificates. Partici ants !ere categori>ed based on the follo!ing definitions: o ti$al 6? =* n$ol@. , ?-+ ng@$l 7, ins#fficient 6*+A=;.<< n$ol@., '+A'<.<< ng@$l7, $oderate deficiency 6'*A;<.<< n$ol@., (+A(<.<< ng@$l7, or se"ere deficiency 6B'* n$ol@., B(+ ng@$l7. Metabolic syndro$e !as defined er the '++< international consens#s

state$ent.

Cey Findings
4f all (,9+( artici ants, only 9D had le"els greater than -+ ng@$l. EF#ally s#r rising, ;'.9D had le"els bet!een (+ and '+ ng@$l, and ''.'D had le"els less than (+ ng@$l. 0n this !hite, Ger$an 6$edically ins#red7 o #lation, only 'D re orted taking any "ita$in s# le$ents at all. The res#lts de$onstrated a ser#$ le"elAde endent red#ction in all-ca#se $ortality 6PB+.++( for trend7 !ith a =*D red#ction in the ha>ard ratio in the artici ants !ith o ti$al "ita$in D le"els relati"e to those !ith se"ere deficiency after f#ll ad1#st$ent 6%2: +.'*8 <*D C0: +.(-A+.;:7. The res#lts also de$onstrated a ser#$ le"elAde endent red#ction in cardio"asc#lar $ortality GPB+.++( for trend8 %2: +.-- 6+.(:A+.::7H. 2isk red#ction incl#ded that by s#dden death 6PB+.++; for trend, %2: +.(*8 <*D C0: +.+;A+.:-7 and congesti"e heart fail#re G%2: +.'; 6+.+:A(.+;7H. The res#lts did not change $arkedly after re$o"ing artici ants !ith ty e 00 diabetes or glo$er#lar filtration rates B:+ $l@$in@(.=- $ '. The res#lts did not change !ith seasonality 6s#$$er@!inter7 nor !ith self-re orted acti"ity le"els. The res#lts did not change significantly !hen eli$inating fro$ the analysis any artici ant !ho died !ithin ' years of follo!-# .

Clinical 0$ lications
This st#dyIs rob#st findings confir$ the strong association of lo! "ita$in D stat#s !ith increased risk of both all-ca#se and cardio"asc#lar $ortality re orted in $#lti le re"io#s st#dies fro$ other large databases, incl#ding those of the Centers for Disease Control and Pre"ention CDC 63ational %ealth and 3#trition E)a$ination S#r"ey7 and of 0nter$o#ntain %ealth 6&tah7. The strengths of this st#dy incl#de the large n#$bers, the biological la#sibility of lo! "ita$in D for ad"erse health conseF#ences, and the strength of the association e"en !hen considering significant confo#nders. The o #lation tested 6!hite, ins#red, #ndergoing electi"e angiogra hy7 is #niF#e for e)isting large databases. 4ne !o#ld e) ect this o #lation to ha"e $#ch higher "ita$in D le"els. More than :*D of the artici ants had "ita$in D le"els belo! the '+(+ 0nstit#te of Medicine 604M7 lo! standard Jnor$alK of '+ ng@$l. Please note that in '+(( the Endocrine Society reco$$ended achie"e$ent of a ser#$ le"el of ;+A:+ ng@$l.( 4nly 9D of the (,9+( artici ants achie"ed a le"el greater than -+ ng@$l. This $eans that a rather $inisc#le n#$ber of artici ants achie"ed the reco$$ended le"el of ;+ ng@$l.

A key point for all future studies: Dosing does not matter. What counts is the serum

level at the start and at the end of the intervention.

Perha s $ost clinically i$ ortant fact for readers is that "ita$in D is a lo!cost, lo!-to)icity inter"ention that co$ le$ents other $edical inter"entions. E"en in the absence of rando$i>ed, controlled trials de$onstrating ca#sality in all-ca#se and cardiac $ortality, er recent a#thoritati"e reco$$endations by the 04M and the &S Pre"enti"e Ser"ices Task Force, clinicians sho#ld ad"ocate for their atientsI good bone health and red#ced risk of falls by ens#ring nor$al "ita$in D le"els. This st#dy strongly s#ggests that additional health benefits are likely to follo!. This st#dy dra!s concl#sions based on 1#st one "ita$in D le"el obtained at the start in a o #lation at increased risk for all-ca#se and cardio"asc#lar $ortality. 2eaders cannot dra! a ca#sal connection. As s#ch, this st#dy affir$s the #rgent need for ros ecti"e, rando$i>ed, controlled trials of "ita$in D for red#ction of all-ca#se and cardio"asc#lar $ortality. A key oint for all f#t#re st#dies: Dosing does not $atter. Lhat co#nts is the ser#$ le"el at the start and at the end of the inter"ention. Any st#dy that fails to assess and re ort these "al#es has li$ited clinical significance for $eeting the needs for an e"idence-based $edicine reco$$endation and therefore a o #lation-!ide "ita$in D reco$$endation.

2eference
(. %olick MF, /inkley 3C, /ischoff-Ferrari %A, et al. Clinical ractice g#ideline. E"al#ation, treat$ent, and re"ention of "ita$in D deficieincy: an Endocrine Society clinical ractice g#ideline. J Clin Endocrinol Metab. '+((8<::(<((-(<-+.