Thursday, 7 March 2013

MS, vascular disease and vitamin D are somewhat related

#MSBlog: Preventing vascular disease may impact on the course of MS; vD supplements may be one way of doing this!

"At the recent IPMSC (International Progressive Multiple Sclerosis Collaborative) meeting in Milan a lot of discussion was centered around the topic of progressive MS and other co-morbidties; i.e. other diseases that may not be associated with MS, but can contribute to its progression. Several attendees suggested that the reason why Simvastatin, a drug that reduces cholesterol and cardiovascular events, including cardiovascular deaths (heart attacks and stroke), works in MS is that it is treating the co-morbidities that contribute to MS progression. Interesting?"

"The following paper confirms that MSers are as likely to suffer from vascular diseases as the general population, which may explain why age is such an important risk factor for disease progression."

Marrie et al. Rising prevalence of vascular comorbidities in multiple sclerosis: validation of administrative definitions for diabetes, hypertension, and hyperlipidemia. Mult Scler. 2012 Sep;18(9):1310-9.

BACKGROUND: Despite the importance of comorbidity in multiple sclerosis (MS), methods for comorbidity assessment in MS are poorly developed.


OBJECTIVE: They validated and applied administrative case definitions for diabetes, hypertension, and hyperlipidemia in MS.

METHODS: Using provincial administrative data they identified MSers and a matched general population cohort. Case definitions for diabetes, hypertension, and hyperlipidemia were derived using hospital, physician, and prescription claims, and validated in 430 MSers. They examined temporal trends in the age-adjusted prevalence of these conditions from 1984-2006.

RESULTS: Agreement between various case definitions and medical records ranged from kappa (κ) =0.51-0.69 for diabetes, κ =0.21-0.71 for hyperlipidemia, and κ =0.52-0.75 for hypertension. The 2005 age-adjusted prevalence of diabetes was similar in the MS (7.62%) and general populations (8.31%; prevalence ratio [PR] 0.91; 0.81-1.03). The age-adjusted prevalence did not differ for hypertension (MS: 20.8% versus general: 22.5% [PR 0.91; 0.78-1.06]), or hyperlipidemia (MS: 13.8% versus general: 15.2% [PR 0.90; 0.67-1.22]). The prevalence of all conditions rose in both populations over the study period.

CONCLUSION: Administrative data are a valid means of tracking diabetes, hypertension, and hyperlipidemia in MS. The prevalence of these comorbidities is similar in the MS and general populations.

"Why are comorbidities important? If they are contributing to disease progression and MS-related mortality then any holistic approach to MS should address these diseases. Which is why the following non-MS-related   vitamin D studies are so important. They are well performed epidemiology studies from Denmark that show low vitamin D levels increase your chances of heart disease and stroke. The implications are that if you keep your vD levels high you may be able to prevent or delay vascular disease. This is another reason why MSers should keep themselves vD replete; most vD experts consider a level between 100-150nmol/L to be optimal."


Brøndum-Jacobsen et al. 25-hydroxyvitamin d levels and risk of ischemic heart disease, myocardial infarction, and early death: population-based study and meta-analyses of 18 and 17 studies. Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2794-802.

OBJECTIVE:  They tested the hypothesis that reduced plasma 25-hydroxyvitamin D associates with increased risk of ischemic heart disease, myocardial infarction, and early death.

METHODS AND RESULTS: They measured baseline plasma 25-hydroxyvitamin D in 10 170 women and men from the Danish general population without vitamin D-fortified food. During 29 years of follow-up, 3100 persons developed ischemic heart disease, 1625 myocardial infarction, and 6747 died. Decreasing plasma 25-hydroxyvitamin D levels were associated with increasing risk of ischemic heart disease, myocardial infarction, and early death as a function of seasonally adjusted percentile categories (P for trend, 2×10(-4)-3×10(-53)). Comparing individuals with plasma 25-hydroxyvitamin D levels at the 1st to 4th percentile with individuals with levels at the 50th to 100th percentile, the multivariable adjusted risk was increased by 40% (95% CI, 14%-72%) for ischemic heart disease, by 64% (25%-114%) for myocardial infarction, by 57% (38%-78%) for early death, and by 81% (40%-135%) for fatal ischemic heart disease/myocardial infarction. In the meta-analyses of 18 and 17 studies, risk of ischemic heart disease and early death were increased by 39% (25%-54%) and 46% (31%-64%) for lowest versus highest quartile of 25-hydroxyvitamin D level.

CONCLUSIONS: They observed increasing risk of ischaemic heart disease, myocardial infarction, and early death with decreasing plasma 25-hydroxyvitamin D levels. These findings were substantiated in meta-analyses.

OBJECTIVE:  They tested the hypothesis that low plasma concentrations of 25-hydroxyvitamin D are associated with increased risk of symptomatic ischemic stroke in the general population.

METHODS: They measured plasma 25-hydroxyvitamin D in 10,170 individuals from the general population, the Copenhagen City Heart Study. During 21 years of follow-up, 1,256 and 164 persons developed ischemic and hemorrhagic stroke, respectively. In a meta-analysis of ischemic stroke, they included 10 studies, 58,384 participants, and 2,644 events.

RESULTS: Stepwise decreasing plasma 25-hydroxyvitamin D concentrations were associated with stepwise increasing risk of ischemic stroke both as a function of seasonally adjusted percentile categories and as a function of clinical categories of 25-hydroxyvitamin D (p for trend ≤ 2 × 10(-3) ). In a Cox regression model comparing individuals with plasma 25-hydroxyvitamin D concentrations between the 1st and 4th percentiles to individuals with 25-hydroxyvitamin D concentrations between the 50th and 100th percentiles, multivariate adjusted hazard ratio of ischemic stroke was 1.82 (95% confidence interval, 1.41-2.34). Comparing individuals with clinical categories of severe vitamin D deficiency (<25.0nmol/l [<10.0ng/ml]) to individuals with optimal vitamin D status (≥75.0nmol/l [≥30.0ng/ml]), the multivariate adjusted hazard ratio of ischemic stroke was 1.36 (1.09-1.70). 25-Hydroxyvitamin D concentrations were not associated with risk of hemorrhagic stroke. In a meta-analysis comparing lowest versus highest quartile of 25-hydroxyvitamin D concentrations, the multivariate adjusted odds ratio of ischemic stroke was 1.54 (1.43-1.65) with a corresponding hazard ratio of 1.46 (1.35-1.58) in prospective general population studies.

INTERPRETATION: In this large population-based prospective study, they observed stepwise increasing risk of symptomatic ischemic stroke with decreasing plasma 25-hydroxyvitamin D concentrations. This finding was substantiated in a meta-analysis.

"Who said this blog was only about MS? If we want to spread the message of a holistic approach to treating MS we need to cover all issues that may impact on your life? This includes vD supplementation. Do you mind doing another quick survey around vD supplementation in your country?"


19 comments:

  1. Well well well, wonders will never cease. I have images of Mrs 'X' who has retrograde blood in her ijv's, this has been confirmed at two centres both blinded to each other's results. I wonder how much damage this has acumulated over the years.

    Regards as always

    ReplyDelete
    Replies
    1. I would also like some of these studies looking into type 2 Diabetes (not 1) if you have any. I think this also might shed some light on the connection.

      Regards as always.

      Delete
    2. MSers are as likely to suffer from vascular diseases as the general population, which may explain why age is such an important risk factor for disease progression.

      Delete
    3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC501826/
      I know we may have been here before, but where does this study fit in ?
      and then is it not just saying

      Delete
    4. Sorry computer went dead and lost my train of thought. I appreciate what you're saying re low vit D driving vascular issues regardless of MS or not and this is increased with age, but you wouldn't be surprised to hear me say I think vascular defects pre date MS.
      I also think with the exception of the VitD link, we've been here before.
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848107/

      Regards as always.

      Delete
    5. As we were about to veer off topic (my fault) and head off into CCSVI land once again (can't think who I'm thinking about here!)I decided to try and get things back on the straight and narrow so I deleted both my comment and your reply.
      Many people here judging by the comments get put off with the same old same old.

      Delete
    6. Part of my answer was to a question posed by Andy and had nothing to do with CCSVI.

      Regarding diabetes type 2:
      "Type 2 diabetes mellitus: A central nervous system etiology"
      http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2010;volume=1;issue=1;spage=31;epage=31;aulast=Jannetta

      Delete
    7. Not read the link yet V V (thanks).

      The reason why I'm curious to find some link with Type 2 Diabetes is because within Mrs X's Family there is a definite hand me down of Type 2 Diabetes to a striking degree.
      This is despite an obvious otherwise fit family and I'm talking a male sibling who was a professional dancer and Father who was still leading D of E Gold expiditions well into his late 60's and all seeming to have an ideal bmi.

      Now the only one ,yes the only one, going back to include Uncle's, Grandparent etc who doesn't have Type 2 diabetes, has an agressive form of ppms. I appreciate this is a very small study group, but nonetheless interesting from what I've seen. Any response I would find interesting, thanks.

      See ,not a mention of CCSVI MD2.

      Regards as always

      Delete
    8. Sorry computer is on a go slow. To bring it back round, what do we know of the link to low Vit D within dibetes, vascular dementia and of course MS ?
      What is the mechanism for some people to have a low Vit D level despite leading similar lives to someone with normal levels ?

      More questions than answers, oh I feel a reggae song coming on.

      Regards as always.

      Delete
  2. With all the talk about vitamin D and/or UV light being helpful in MS, why don't neurologists prescribe UVB lamps for MSers such as what's used for psoriasis?

    ReplyDelete
    Replies
    1. Without class 1 evidence and a licence from the EMA or FDA who is going to pay for the lamps? That is the reality of the current era; we need to have at least 2 randomised double-blind placebo- or sham-controlled trials to show that something works before the payers will pay.

      Delete
    2. Ok that answers why neurologists wouldn't prescribe them.
      But when no one is doing the trials, it is frustrating. I can get my hands on a UVB lamp. It's been a long winter. It seems logical. For whatever reasons supplementing with vitamin D doesn't get my levels to go up. It's a legitimate question: as patients should we be concerned about class 1 evidence, or should we try the things that seem logical if they are low risk?

      Delete
  3. Good post Andy Clarke, I was also wondering like yourself how this sat with the findings of the vascular co-morbidity report of 2010.
    http://www.ncbi.nlm.nih.gov/pubmed/20350978

    ReplyDelete
  4. Re: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC501826/

    read this: http://en.wikipedia.org/wiki/Andrew_Wakefield

    ReplyDelete
    Replies
    1. Hunt through the posts so hear about my sleepless nights on this one

      Delete
  5. It was only by reading this blog that I was really alerted to the VitD research data. I decided to ask my GP for a test and was found to be 'low' verging on 'very low'. After 4 months' supplementation (400u per day), after which my levels rose, I decided to self-medicate and have taken 5,000u daily ever since. I am hoping that my neuro will approve, because my GP says she is happy to prescribe whatever dosage he recommends. I would like my VitD to be on prescription if only because my levels would then (presumably) be monitored. When I saw my neuro last (14 months ago), he said it was fine to supplement but that it wouldn't affect the MS. I'm wondering if he will have changed his stance in the interim. What I couldn't have predicted is that since I started taking VitD, my long-standing back pains(poor gait resulting in slipped disc, sciatica, discectomy)have improved vastly. Hitherto I was taking diclofenac and strong painkillers 2/3 times a week - now once a fortnight or less. How amazing is that - and couldn't that be helpful to a lot of MSers with similar musculo-skeletal problems?

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  6. Hello, I find vascular connection with MS very, very interesting. I found many papers (before I knew anything about CCSVI) about things relating to vascular issues, bbb, endothelial, flow etc. Interesting papers like Adams paper (-88):
    http://koti.mbnet.fi/hiihoo/ccsvi/Adams%20vascular%20damage%20MS%2088.pdf

    My common sense says, that this is one, very important area of research among others, one piece of complicated MS puzzle.

    ReplyDelete

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