Two new studies suggest that vitamin D and vitamin C have important roles to play in cardiovascular health, and should not be overlooked.

Both studies were published in high-profile mainstream medical journals, and reflect the growing awareness within mainstream medicine that there is far more to the cardiovascular disease process than cholesterol elevation.

This shift in perspective couldn’t be more timely, in light of the recent findings from the ENHANCED study showing that lowering LDL with the combination anti-cholesterol drug Vytorin, did nothing to slow or reverse atherosclerotic plaque build-up (and presumably risk of MI).

In January, Thomas Wang, MD, and colleagues at Massachusetts General Hospital published data showing that vitamin D deficiency increased the odds of CV events in a cohort of 1,739 middle-aged, white subjects participating in the Framingham Offspring Study. These people had a mean age of 59, and showed no evidence of cardiovascular disease at baseline. But after a mean follow-up of 5.4 years, 120 people (6.9%) had a first CV event. Those who were vitamin D deficient were much more likely to be among that heart attack subset.

The investigators actually measured 25-dihydroxyvitamin-D (25-OHD), and found that 28% had levels below 15 ng/ml, characterized as mild deficiency; 9% of the cohort was frankly deficient with 25-OHD levels below 9 ng/ml.

D-ficiency Equals Risk

After adjusting for all other conventional CV risk factors, Dr. Wang found a hazard ratio for CV events of 1.62 for individuals with 25-OHD levels below 15, suggesting a 62% increase in risk. For those who were also hypertensive, the hazard ratio was 2.13, more than double the risk of normotensive people with adequate vitamin D levels. People with OHD levels under 10 ng/ml had a hazard ratio of 1.8, or an 80% increased risk (Wang TJ, et al. Circulation. 2008; 117(4): 503–511).

The MGH researchers also saw a graded increase in CVD risk as levels of vitamin D decreased. Further adjustment for C-reactive protein, physical activity level, or supplement use did not change the findings.

Because the Wang study was prospective, it provides some much-needed bolstering of findings from smaller cross-sectional studies showing associations between vitamin D deficiency and myocardial infarction, stroke and heart failure.

The authors suggest that vitamin D is involved in regulation of the renin-angiotensin axis. Given the widespread distribution of vitamin D receptors in the endothelial lining of the entire vascular tree, and in the cardiomyocytes, it probably also plays a role in regulating vascular smooth muscle. It may also reduce endothelial inflammation and thrombosis.

Can Supplementation Help?

The big question, which this study was not designed to answer, is whether vitamin D supplementation mitigates the observed risk. It is certainly reasonable to think it would, and several small studies have shown that vitamin D can reduce blood pressure, left ventricular hypertrophy and levels of circulating inflammatory cytokines, all of which point to reduced risk of actual cardiac events.

Dr. Wang noted that in the Women’s Health Initiative, vitamin D supplementation did not reduce CVD events. But he pointed out that WHI was a bone-fracture prevention study, and not designed to assess CV risk or the impact of vitamins on it. He added that the vitamin D doses used in WHI were far below levels needed to correct frank deficiencies. Further, women in the placebo arm were permitted, though not required to take vitamins, which could have masked the potential CV benefit of the vitamin D.

In short, the data from WHI are hardly conclusive and do not support a categorical dismissal of vitamin D as a heart disease preventive. At the same time, this new study, while clearly showing vitamin D deficiency equals increased risk, is not definitive evidence in favor of supplementation.

Still, Dr. Wang believes the findings have “potentially broad public health implications, given the high prevalence of vitamin D deficiency in developed countries, the contribution of lifestyle and geography to vitamin D status, and the ease, safety and low cost of treating vitamin D deficiency.”

(For more perspective on vitamin D and chronic diseases, visit www.holisticprimarycare.net and read Better Bones & Beyond: Vitamin D Is Key in Preventing Inflammatory & Metabolic Diseases.)

High C, Low Stroke

The role of Vitamin C in cardiovascular health has been the subject of controversy for decades. While the debate will likely rage for some time to come, public health researchers at the University of Cambridge recently published a paper showing a strong inverse correlation between serum vitamin C and likelihood of stroke.

The study was part of the European Prospective Investigation into Cancer (EPIC)–Norfolk project, an ongoing, large-scale population-based study of risk factors for cancer and other diseases.

Dr. Phyo Kyaw Myint and colleagues collected baseline plasma vitamin C levels from 20,649 men and women, aged 40–79 years, participating in the EPIC study. All were initially seen during the years 1993–1997, and followed until March 2005. During that time, there were 448 incident strokes within the study cohort (2.2% incidence).

Cox proportional hazards analysis showed that people in the top quartiles of baseline plasma vitamin C concentrations had a 42% lower risk of stroke (relative risk: 0.58; 95% CI: 0.43, 0.78) than did those in the bottom quartile. This finding was independent of age, sex, smoking status, BMI, blood pressure, cholesterol level, physical activity, diabetes or history of myocardial infarction. Interestingly, it was also independent of social class, alcohol consumption, or reported use of supplements.

The authors reported the same degree of Vitamin C-associated stroke risk reduction after excluding individuals with pre-existing illnesses, users of ascorbic acid-containing supplements, and those who had had early strokes during the initial two years of follow-up (Myint PK, et al. Am J Clin Nutr. 2008; 87(1): 64–69).

The observation that taking vitamin C did not appear to change the risk profile led Dr. Myint to the notion that the observed correlation between high vitamin C levels and low stroke risk is a reflection of overall dietary habits, with the plasma C levels being an indicator of a diet rich in fruits and vegetables, the primary sources of this and other vitamins.

In other words, plasma vitamin C is a marker of overall dietary health; those who eat a plant-rich diet will tend to have higher plasma vitamin C levels, along with higher levels of many other vitamins, minerals and antioxidant compounds. These, in aggregate, are what collectively reduce the vascular risk.

In an editorial accompanying Dr. Myint’s report, Drs. Sebastian Padayatty and Mark Levine of the National Institute of Diabetes and Digestive and Kidney Diseases, encouraged doctors to keep an eye on their patients’ plasma vitamin C levels as a “readily measurable and reliable biomarker” of fruit and vegetable intake and thus a good indicator of someone’s general nutritional status.