Looking for input
Does anyone use Vit D as part of coronary prevention? Is there any experience out there that we can learn from?

This study demonstrated a >30% reduction in heart attacks in the group taking Vit D. If this is true, Vit D competes with statins for efficacy.

This study is 5 years old and in my experience mostly ignored. Any thoughts out there?

additionally
From a standpoint of just prevalence of Vit D deficiency, it's really common here in South Central Kentucky. Our endocrinologist said when she moved here, she was astounded by it. I'd bet it's more prevalent since women moved into the work place over the past 40 years, out of the sunlight and into the office.
I was astounded that I essentially had no vitamin D a couple of years ago. For no other reason than osteoporosis prevention and therapy, we should urge our patients to ask their FP's about it.
Melissa

additionally
There is a trial out of the US someplace which found that combination vitamin D and calcium prevented cancer. On the basis of this study, here in Ontario cancer guidelines changed to recommend vitamin D and calcium in all postmenopausal women; it was a profound announcement. After I reviewed the trial, I was much less impressed, but I must admit, I do not know alot about the vitamin D, cancer literature.

nnt in ca study
In the womens study, nonskin cancer was reduced by 77% over 4 years for women over 55. ARR 5% with NNT 20. ie treat 20 women over 55 for 4-5 years with vit d and prevent one cancer. wow

The Health Professionals Follow-up Study N=47,800 men 1986-2000 found low levels of vitamin D were associated with increased incidence of cancer and mortality

More please...............
Michael,
What was that study design? primary endpoints? Followup? In what journal? What institution?
Melissa

The Jrnl of Family Practice 56(11);907-910
The results of the study, conducted between 2000 and 2005, were reported in the June 8 online edition of the American Journal of Clinical Nutrition.

“The findings are very exciting. They confirm what a number of vitamin D proponents have suspected for some time but that, until now, have not been substantiated through clinical trial,” said principal investigator Joan Lappe, Ph.D., R.N., Creighton professor of medicine and holder of the Criss/Beirne Endowed Chair in the School of Nursing. “Vitamin D is a critical tool in fighting cancer as well as many other diseases.”

not vitamin D, but still worrisome
BMJ, doi:10.1136/bmj.39440.525752.BE (published 15 January 2008)

Research
Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial
Mark J Bolland, research fellow1, P Alan Barber, senior lecturer1, Robert N Doughty, associate professor1, Barbara Mason, research officer1, Anne Horne, research fellow1, Ruth Ames, research officer1, Gregory D Gamble, research fellow1, Andrew Grey, associate professor1, Ian R Reid, professor1

1 Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand

Correspondence to: I R Reid i.reid@auckland.ac.nz

Abstract
Abstract
Introduction
Methods
Results
Discussion
References

Objective To determine the effect of calcium supplementation on myocardial infarction, stroke, and sudden death in healthy postmenopausal women.
Design Randomised, placebo controlled trial.

Setting Academic medical centre in an urban setting in New Zealand.

Participants 1471 postmenopausal women (mean age 74): 732 were randomised to calcium supplementation and 739 to placebo.

Main outcome measures Adverse cardiovascular events over five years: death, sudden death, myocardial infarction, angina, other chest pain, stroke, transient ischaemic attack, and a composite end point of myocardial infarction, stroke, or sudden death.

Results Myocardial infarction was more commonly reported in the calcium group than in the placebo group (45 events in 31 women v 19 events in 14 women, P=0.01). The composite end point of myocardial infarction, stroke, or sudden death was also more common in the calcium group (101 events in 69 women v 54 events in 42 women, P=0.008). After adjudication myocardial infarction remained more common in the calcium group (24 events in 21 women v 10 events in 10 women, relative risk 2.12, 95% confidence interval 1.01 to 4.47). For the composite end point 61 events were verified in 51 women in the calcium group and 36 events in 35 women in the placebo group (relative risk 1.47, 0.97 to 2.23). When unreported events were added from the national database of hospital admissions in New Zealand the relative risk of myocardial infarction was 1.49 (0.86 to 2.57) and that of the composite end point was 1.21 (0.84 to 1.74). The respective rate ratios were 1.67 (95% confidence intervals 0.98 to 2.87) and 1.43 (1.01 to 2.04); event rates: placebo 16.3/1000 person years, calcium 23.3/1000 person years. For stroke (including unreported events) the relative risk was 1.37 (0.83 to 2.28) and the rate ratio was 1.45 (0.88 to 2.49).

Conclusion Calcium supplementation in healthy postmenopausal women is associated with upward trends in cardiovascular event rates. This potentially detrimental effect should be balanced against the likely benefits of calcium on bone.

calcium article cut and paste
http://www.bmj.com/cgi/content/full/bmj.39440.525752.BEv1

Could it have the same signal for risk that rosiglitazone has???? :o)

This is actually a very interesting study and had a lot of exclusions when you read the paper. 400 mg ca in am, 600 mg in pm.

if they had low vit d they were excluded. elderly pop, more than 10% over 80. etc.. etc.. it is prococative.

Ca article
I have printed it off and will dissect it for you.

caveats
1) Sample restriction. The patients were mainly older white Australian women (mean age 74) with quite high baseline cholesterol (LDL 4.26 and 4.39 mmol/L).

2) There was an imbalance in that risk factors were more prevalent in the treatment group (current smoking, former smoking, hypertension, ischemic heart disease, previous dyslipidemia, previous stroke or TIA). That's worrisome.

3) The sample size is small so the 95% CI are wide.

4) The endpoint analysis was secondary (but preplanned).

5) 10% of women did not have complete follow-up - did these cluster all in one group? hmmm. not reported.

6) After looking only at adjudicated outcomes (Table 4), statistical significance for all but the composite was lost.

7) Most telling to me, after adjusting for many of the baseline imbalances in a large multivariate model, the p value for calcium on events was no longer significant, whereas the baseline variables that were differentially assorted by randomization were quite significant (eg, history of CVD, p=.0001; history of IHD p=.04). This suggests to me that it may be baseline imbalances in a smaller randomized trial that is driving this.

provocative
Dan, this is interesting and adds to prior data: Iowa and Boston benefit, UK no benefit.. etc..

Keep in mind this is a SECONDARY analysis and must be interpreted with caution.

also the ca group had higher baseline levels of the following (uncertain if 95% confidence levels):

TC
LDL
Current smokers
Former smokers
SBP 1 mm hg higher
DBP 1 mm hg higher
Hx of HTN
Hx of ishcemic CHD
Hx of dyslipidemia
Hx of prior stroke/TIA

this looks pretty complicated when you have a group of 74 yo women and do a secondary analysis and the group that has events has much more cumulative risk as above.

I'm quite the skeptic when these aren't primary analyses or perfectly matched groups. good media though.

actually multivariable + randomization is solid
Doing a multivariable analysis on a randomized trial is the best way to correct for imbalances, and should be done more often. They should have put in many more variables. Epidemiologically this is an extremely sound approach, since it adjusts for chance bias.

Input for William Blanchet
I believe that Dr. William Davis, MD, FACC, is among the experts in using vitamin d supplementation as part of coronary artery disease prevention.

Over the last 2 years, he has become increasingly insistent on it's importance not just for prevention but for regression of coronary artery plaque among his patients.

He wrote a review article about it here:



His blog posts about it are here:



As I understand it, he will be presenting data concerned with his coronary plaque regression experience at a conference in the spring 2008.

haven't we seen this all b4?
- vit E supplements linked to lower CHD rates

- trials then show that vit E increases mortality

- i agree with davie - drugs guilty til proven innocent

- don't jump the gun yet!

more please
N. Estrada,
What conference ?

Dan, I believe you have a point. I think Zetia has a lot more weight of literature to gleen "no harm from" than Vitamin D, though both are ailing in the efficacy category for event reduction.
Melissa

guilty
so unfortunate - i thought our society was based on innocent until proven guilty. i understand the risk rewards we face in all medical interventions every day.

it's like saying bb's are bad again. it really shows how people can make poor conclusions based on meta-analysis, retrospective analysis, secondary analysis and studies applied to different populations then our 'average' patients.

that is why ncep, atpiii, ada, aha etc are so conservative with recs - there must be an overwhelming body of evidence before major recs are given.

vit d 1000 iu is now rec for maintenance of health by rda governing bodies. I think that is reasonable based on a wealth of evidence. even Canada is rec this for god's sake (in jest bcuz canada has prevention programs that could be rec as much better than us) :o) mc

Davis presentation of data in Spring 2008
Melissa Walton-Shirley,

I read that he would be making such a presentation in the TheHeart org forum thread entitled "DES showdown: Serruys vs Virmani".

His post in that thread talking about such a presentation was entitled "Vitamin D and coronary artherosclerosis".

He recommends supplementing, not to a particular dose, but to a vitamin D3 blood level: 50-60 ng/mL.

In my last post, I put in a link to an article Dr. Davis wrote about Vitamin D published last fall but the link didn't get posted.

Davis presentation of data in Spring 2008
Melissa Walton-Shirley,

I read that he would be making such a presentation in the TheHeart org forum thread entitled "DES showdown: Serruys vs Virmani".

His post in that thread talking about such a presentation was entitled "Vitamin D and coronary artherosclerosis".

He recommends supplementing, not to a particular dose, but to a vitamin D3 blood level: 50-60 ng/mL.

In my last post, I put in a link to an article Dr. Davis wrote about Vitamin D published last fall but the link didn't get posted.

evidence based medicine vs dogma based medicine
The use of vitamin D to stave off coronary artery disease or stroke does not seem to me to be evidence-based. All of the trial data that I have seen to date has been negative. I am keeping an open mind and hoping someone will post an abstract of a trial I might have missed.

isn't dogma a ben affleck movie
Circulation. 2007 Feb 20;115(7):846-54. low doses were used, new rec is now 1000 IU/day

Arch Intern Med. 2007 Sep 10;167(16):1730-7


Am J Clin Nutr. 2006 Apr;83(4):754-9. provocative.

Prog Biophys Mol Biol. 2006 Sep;92(1):65-79. Epub 2006 Feb 28. perhaps some of these sources can help as well as those above.

It would be interesting to see if vit d was safer and more effective than basa for cv event reduction. We agree with current guidelines that 1000 IU vit d is the appropriate amount whether dietary or supplemental.

there are so many expensive, poor evidence based strategies currently being employed in medicine - it just seems that vit d is inexpensive, easy and will help 30-40% of people who have low serum levels anyway. that's our clinical decision.

clarification
are these RCTs with hard endpoints showing that vitamin D prevents cardiovascular events?

D
i listed those articles so you can look them up, read them, look at the references, come to your own clinical decision.

the body of evidence supports generally better health with currently rec 1000 iu/day of vit d.

good luck

ps. what i can tell you is for those pts in our clincial practice with low vit d values (based on lab draw), - they have noted significant morbidity sx reduction with tx and we hope they will see the 77% ca reduction and trend or better for cv events.

mort
Arch Intern Med. 2007 Sep 10;167(16):1730-7.

Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials.Autier P, Gandini S.


BACKGROUND: Ecological and observational studies suggest that low vitamin D status could be associated with higher mortality from life-threatening conditions including cancer, cardiovascular disease, and diabetes mellitus that account for 60% to 70% of total mortality in high-income countries. We examined the risk of dying from any cause in subjects who participated in randomized trials testing the impact of vitamin D supplementation (ergocalciferol [vitamin D(2)] or cholecalciferol [vitamin D(3)]) on any health condition. METHODS: The literature up to November 2006 was searched without language restriction using the following databases: PubMed, ISI Web of Science (Science Citation Index Expanded), EMBASE, and the Cochrane Library. RESULTS: We identified 18 independent randomized controlled trials, including 57 311 participants. A total of 4777 deaths from any cause occurred during a trial size-adjusted mean of 5.7 years. Daily doses of vitamin D supplements varied from 300 to 2000 IU. The trial size-adjusted mean daily vitamin D dose was 528 IU. In 9 trials, there was a 1.4- to 5.2-fold difference in serum 25-hydroxyvitamin D between the intervention and control groups. The summary relative risk for mortality from any cause was 0.93 (95% confidence interval, 0.87-0.99). There was neither indication for heterogeneity nor indication for publication biases. The summary relative risk did not change according to the addition of calcium supplements in the intervention. CONCLUSIONS: Intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates. The relationship between baseline vitamin D status, dose of vitamin D supplements, and total mortality rates remains to be investigated. Population-based, placebo-controlled randomized trials with total mortality as the main end point should be organized for confirming these findings.

Point of clarification, please
Were the references posted by N Estrada intentionally erased or did they just not transmit? If they were intentionally removed, what is the explanation for this?

Forum raptors
William,
I never saw those posts, but if the "poster" has a history of grinding an axe at every opportunity with a well hashed out redundant arguement , he or she might get edited. It's common place for herbalists, main stream med haters, hidden agenda posters to try to get on our site every now and then. I have no patience for Velocoraptors.....those who bate and then attack from the side who know their only advantages are suprise and strength in number, not fact. I don't respect that and am glad for our editor to hit the ejector , or should I more correctly say, the "extinction" button.
Most folks just express opinion and debate openly and honorably, others don't. If they've been guilty repeatedly of this in the past, we have no patience for them.
As for Vit D, there is no trial with hard endpoints that show a reduction in cardiovascular mortality in patients with normal levels. I think common sense (though be careful here), dictates a need for correction of Vit D levels for osteoporosis protection, but no prospective double blind study has been designed in "normal level" patients to look at CV risk reduction. I hope it works, but until we see a trial such as this, I'm afraid we can't make a firm recommendation for this treatment to the masses.
It pays to agree to disagree, discuss respectfully and always try to make your point,............ but don't ever be a raptor. (tongue in cheek!)

Melissa

Nope
No posts have been deleted from this thread.

there has been
Melissa, there was a neg. trial in Circulation published earlier this year, with hard endpoints.

trial
Cardiovascular Disease in Women


Calcium/Vitamin D Supplementation and Cardiovascular Events
Judith Hsia, MD; Gerardo Heiss, MD, PhD; Hong Ren, MS; Matthew Allison, MD, MPH; Nancy C. Dolan, MD; Philip Greenland, MD; Susan R. Heckbert, MD, PhD; Karen C. Johnson, MD, MPH; JoAnn E. Manson, MD, DrPH; Stephen Sidney, MD, MPH; Maurizio Trevisan, PhD, for the Women’s Health Initiative Investigators
From the Department of Medicine, George Washington University, Washington, DC (J.H.); Department of Epidemiology, University of North Carolina School of Public Health, Chapel Hill (G.H.); Fred Hutchinson Cancer Research Center, Seattle, Wash (H.R.); Department of Family and Preventive Medicine, University of California at San Diego, San Diego (M.A.); Departments of Medicine (N.C.D., P.G.) and Preventive Medicine (P.G.), Northwestern University, Chicago, Ill; Department of Epidemiology, University of Washington, Seattle (S.R.H.); Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis (K.C.J.); Division of Preventive Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass (J.E.M.); Kaiser Permanente, Oakland, Calif (S.S.); and University at Buffalo School of Public Health and Health Professions, Buffalo, NY (M.T.).

Correspondence to Judith Hsia, MD, 2150 Pennsylvania Ave, NW No. 4–414, Washington, DC 20037. E-mail jhsia{at}mfa.gwu.edu

Received November 2, 2006; accepted December 14, 2006.

Background— Individuals with vascular or valvular calcification are at increased risk for coronary events, but the relationship between calcium consumption and cardiovascular events is uncertain. We evaluated the risk of coronary and cerebrovascular events in the Women’s Health Initiative randomized trial of calcium plus vitamin D supplementation.

Methods and Results— We randomized 36 282 postmenopausal women 50 to 79 years of age at 40 clinical sites to calcium carbonate 500 mg with vitamin D 200 IU twice daily or to placebo. Cardiovascular disease was a prespecified secondary efficacy outcome. During 7 years of follow-up, myocardial infarction or coronary heart disease death was confirmed for 499 women assigned to calcium/vitamin D and 475 women assigned to placebo (hazard ratio, 1.04; 95% confidence interval, 0.92 to 1.18). Stroke was confirmed among 362 women assigned to calcium/vitamin D and 377 assigned to placebo (hazard ratio, 0.95; 95% confidence interval, 0.82 to 1.10). In subgroup analyses, women with higher total calcium intake (diet plus supplements) at baseline were not at higher risk for coronary events (P=0.91 for interaction) or stroke (P=0.14 for interaction) if assigned to active calcium/vitamin D.

Conclusions— Calcium/vitamin D supplementation neither increased nor decreased coronary or cerebrovascular risk in generally healthy postmenopausal women over a 7-year use period.

Clarifying Dr. Davis' position on Vitamin D3
Dr. Davis does not maintain that Vitamin D3 regresses coronary plaque all by itself or in all patients.

A post he made in that "DES showdown: Serruys vs Virmani" thread I referenced earlier summarized his experience and is quoted in full and with change below the line.

--------------------------------

Heart scan score reduction
The approach is relatively simple:

1) Target LDL (Friedewald) 60 mg/dl; target HDL 60 mg/dl; target triglycerides 60 mg/dl: 60-60-60.

2) Correction of lipoprotein abnormalities, including intermediate-density lipoprotein, lipoprotein(a). (I rely a lot on NMR for lipoprotein analysis.) LDL particle number of <700 nmol/l and/or apoprotein B 60 mg/dl is also targeted.

3) Correction of all phenomena of insulin resistance, including blood glucose.

4) Correction of blood pressure both at rest and with exercise.

5) Correction of serum 25-OH-vitamin D3 levels to 50 ng/ml.

This approach does not guarantee presumed coronary plaque regression using a CT coronary calcium score surrogate, but does weigh the odds heavily in favor of doing so. Also, events are essentially eliminated.

correction
A sentence in my prior post should have read:

A post he made in that "DES showdown: Serruys vs Virmani" thread I referenced earlier summarized his experience and is quoted in full and withOUT change below the line.