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

VitaminDWiki merged two of the tables.

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

See also VitaminDWiki

• Criteria to associate a health problem with low vitamin D
  if more than 7 of 22 features are evident then VitaminDWiki suspect the health probulem is associated with vitamin D
• Overview Cardiovascular and vitamin D
  There are many indications that vitamin D can both PREVENT and TREAT many cardiovascular problems
• Cardiovascular category listing with associated searches
• All items in Cardiovascular and Vitamin D 474 items
• All items in category Hypertension 159 items
• All items in category Strokes and Vitamin D 111 items
• All items in category Metabolic Syndrome and Vitamin D 97 items

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