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Cardiovascular Disease is associated with lack of Vitamin D - meets most of Hill's Criteria -Aug 2014

Does Sufficient Evidence Exist to Support a Causal Association between Vitamin D Status and Cardiovascular Disease Risk? An Assessment Using Hill’s Criteria for Causality

nutrients, ISSN 2072-6643
Patricia G. Weyland William B. Grant and Jill Howie-Esquivel
Department of Physiological Nursing, School of Nursing, University of California, San Francisco (UCSF), #2 Koret Way Box 0610, San Francisco, CA 94143, USA; E-Mail: jill.howie-esquivel at nursing.ucsf.edu
Sunlight, Nutrition, and Health Research Center, P.O. Box 641603, San Francisco, CA 94164-1603, USA; E-Mail: wbgrant at infionline.net
* Author to whom correspondence should be addressed; E-Mail: patricia.weyland at ucsf.edu; Tel.: +1-831-420-7324.
Received: 22 May 2014; in revised form: 31 July 2014 /Accepted: 18 August 2014 / Published: 2 September 2014

Serum 25-hydroxyvitamin D (25(OH)D) levels have been found to be inversely associated with both prevalent and incident cardiovascular disease (CVD) risk factors; dyslipidemia, hypertension and diabetes mellitus.
This review looks for evidence of a causal association between low 25(OH)D levels and increased CVD risk.
We evaluated journal articles in light of Hill’s criteria for causality in a biological system.
The results of our assessment are as follows.

  • Strength of association: many randomized controlled trials (RCTs), prospective and cross-sectional studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors.
  • Consistency of observed association: most studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors in various populations, locations and circumstances.
  • Temporality of association: many RCTs and prospective studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors.
  • Biological gradient (dose-response curve): most studies assessing 25(OH)D levels and CVD risk found an inverse association exhibiting a linear biological gradient.
  • Plausibility of biology: several plausible cellular-level causative mechanisms and biological pathways may lead from a low 25(OH)D level to increased risk for CVD with mediators, such as dyslipidemia, hypertension and diabetes mellitus.
  • Experimental evidence: some well-designed RCTs found increased CVD risk factors with decreasing 25(OH)D levels.
  • Analogy: the association between serum 25(OH)D levels and CVD risk is analogous to that between 25(OH)D levels and the risk of overall cancer, periodontal disease, multiple sclerosis and breast cancer.

Conclusion: all relevant Hill criteria for a causal association in a biological system are satisfied to indicate a low 25(OH)D level as a CVD risk factor.

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Tables in the PDF

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VitaminDWiki merged two of the tables.

Criteria Proposed Vitamin D Mechanism Satisfied?
Strength of associationIs there a large difference in the outcome between
exposed and non-exposed persons?
ConsistencyHas the outcome been observed by multiple researchers,
in various circumstances, places and at different times?
TemporalityDoes the cause always precede the effect? Yes
Biological GradientIs there a dose-response curve? Yes
Blunts renin-angiotensin system
Arterial stiffness (HTN)
Reduced risk of DM
Insulin resistance
PlausibilityIs the suspected causation consistent with
current knowledge of biology?
Glucose regulation Yes
Seasonal variations in serum 25(OH)D
Metabolic syndrome
DM type 2 and its progression
Blood pressure reduction
Blunts renin-angiotensin system
ExperimentHas an observed association led to a
preventive action that has prevented the outcome?
Arterial stiffness (PWV) Insulin resistance Yes
LipidsMetabolic syndrome
AnalogyIs there an analogous exposure and outcome?Cancer DM type 2Yes
Nitric oxide liberated by solar UV
Calcium supplementation
Reverse causation

See also VitaminDWiki

The TOP articles in Cardiovascular and Vitamin D are listed here:

Pages listed in BOTH the categories Cardiovascular and Meta-analysis

Pages listed in BOTH the categories Intervention and Cardiovascular

Attached files

ID Name Comment Uploaded Size Downloads
4341 CVD Hill T3.jpg admin 03 Sep, 2014 141.41 Kb 948
4339 CVD Hill T2B.jpg admin 03 Sep, 2014 37.63 Kb 985
4338 CVD Hill T2A.jpg admin 03 Sep, 2014 61.77 Kb 1125
4336 Cardiovascular Hills criteria.pdf admin 03 Sep, 2014 262.41 Kb 1024