Summary of Findings.
 
  • The further from the equator, the higher the risk of cardiovascular disease including hypertension, heart failure, myocardial infarction and death from cardiovascular disease. (65,66)
 
  • A strong correlation has been shown between vitamin D deficiency and the risk of heart attacks. (75)
 
  • Two large prospective studies have shown that patients with low vitamin D levels have a 200% increase in risk of myocardial infarction and death from cardiovascular disease. (8788)
 
 
Background
 
Living at higher latitudes increases the risk of hypertension and cardiovascular disease. (65, 66) A number of epidemiological studies have shown cardiovascular morbidity and mortality are 30-50% higher in areas of lower sun exposure caused by season or latitude. (72,73)  
 
Deaths from cardiac disease are also highest in the winter months. (74) All of these epidemiological studies point to vitamin D as a causative factor as levels are lower the further north of the equator one lives due to less exposure to ultraviolet radiation.
 
In later studies actual levels of vitamin D were measured and it was confirmed that myocardial infarction patients had lower vitamin D levels that control subjects. Those with low vitamin D levels had an almost 60% greater risk of suffering a heart attack than those with the highest levels. (75)
 
In another study involving 15000 participants the prevalence or hypertension, diabetes and raised triglycerides were significantly higher in those with the lowest concentration of vitamin D (76). 
 
Then it was shown in a subgroup of patients in the Framingham heart study that those with vitamin D3 levels  <15ng/ml had a 60% greater incidence of cardiac events than those with higher levels (77)
 
It has been shown that Statin drugs (used for lowering cholesterol) exert their effect, at least in part, by increasing levels of vitamin D. After 12 months of treatment with a Statin vitamin D levels are increased by 57-75%. (78) 
 
In keeping with this finding it has also been shown that women on statin therapy have a higher bone density which is presumably mediated through elevation of vitamin D and hence improved calcium absorption. (79)
 
Hypertension 
 
Animal studies have shown that vitamin D deficiency activates the rennin-angiotensin system resulting in high blood pressure and cardiac hypertrophy (enlargement of the heart)(80)
 
In the Nurses Professionals Health Study those with low vitamin D levels (<15ng/ml) and who had normal blood pressures at the time of entry had a major increase in their risk of developing hypertension during the follow up period.  Men had a 6 fold increase and women nearly a 3 fold increase in their risk of hypertension. (81) 
 
In a study where hypertensive patients were exposed to ultraviolet light three times per week for three months their blood pressure normalized, both systolic and diastolic pressure was reduced by 6mm Hg, and their vitamin D levels increased by 180%.(67) At least two other studies have been conducted where vitamin D has been used to treat hypertension and shown an approximately 10% reduction in blood pressure. (82,83) 
 
Vitamin D deficiency is also associated with congestive heart failure (65) and has been shown to normalize impaired myocardial contractility seen in experimental vitamin D deficiency. (68) Other preclinical studies have shown that vitamin D prevents thrombus formation, smooth muscle proliferation (69,70) and prevents  arterial calcification(71)
 
Several studies were conducted in the 1990’s to determine the effectiveness of vitamin D replacement therapy on heart disease outcomes. However these studies were conducted when 200IU of vitamin D was thought to be an effective dose. We now know that literally thousands of units/day is needed to significantly affect serum levels in the depleted patient.  So those intervention studies were generally negative due to insufficient dosing.  (84,85)
 
However dramatic effects on survival have been seen in patients with chronic kidney disease when treated with vitamin D. Patients with kidney disease are unable to complete the production of active vitamin D and are therefore grossly deficient. Patients with renal disease and treated with vitamin D or its analogs have shown a 20% decrease in mortality. (86)
 
Recent Studies.
 
In the last twelve months two major studies have been published that convincingly demonstrated that low vitamin D levels are connected to cardiac death.  These two studies are significant in that blood levels of vitamin D were measured at baseline and the subjects then followed for many years. 
 
One of the studies was conducted in male health care professionals in the USA. Those with vitamin D levels in the deficient range compared to those in the sufficient range had a 200% increase in risk of myocardial infarction.  (87) 
 
A similar prospective study was conducted in Germany. In this study patients who were already cardiac patients and who were being admitted for cardiac catheterization studies had their vitamin D levels measured and were then followed up for an average of 7.7 years. Again those patients with vitamin D levels in the lowest quartile compared to those in the highest quartile had over a 200% increase in their risk of death. (88)
 
An excellent review of all the data on cardiovascular effects of vitamin D deficiency was presented by Dr James O’Keefe MD in the Journal of the American College of Cardiology in late 2008.(89) The article is not available unless you subscribe to the journal but copies can be obtained direct from the author at the following email address:  Dr. James O'keefe  jhokeefe@cc-pc.com]
 
Some will still argue that a cause and effect relationship between vitamin D and cardiovascular death has not been established as prospective placebo controlled trials have not been conducted.  While this is true, when a correlation holds true in multiple populations around the world and a dose response can be demonstrated i.e. the lower the level of vitamin D the greater the risk, the chances that the correlation will not hold up is remote. 
 
Such concerns about establishing a cause and effect relationship are justified when one is considering treating a patient with a drug as all drugs have side effects and it is not ethical or desirable to subject patients to side effects if there is no proven effect. 
 
However in the case of vitamin D we are talking about a deficiency disease. There is no down side to having an optimal level of vitamin D as nature intended us to have.
As Dr O’Keefe correctly mentions in the summary of his paper “Large randomized controlled trials are needed to firmly establish the relevance of vitamin D status to cardiovascular health. In the meanwhile, monitoring serum 25- hydroxyvitamin D levels and correction of vitamin D deficiency is indicated for optimization of musculoskeletal and general health”. 

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    Heart Disease and Vitamin D3 Deficiency
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