Low childhood vitamin D linked to adult atherosclerosis
Low levels of 25-OH vitamin D in childhood were associated with subclinical atherosclerosis over 25 years later in adulthood, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.
The importance of vitamin D for cardiovascular health has been the focus of increasing interest. Low levels of vitamin D have previously been shown to be related to increased risk of stroke and heart attack. Vitamin D deficiency and insufficiency are highly prevalent among children worldwide, and this study examined the relationship between low childhood vitamin D levels and adult increased carotid intima-thickness (IMT). IMT is a marker of structural atherosclerosis, which correlates with cardiovascular risk factors, and predicts cardiovascular events.
"Our results showed an association between low 25-OH vitamin D levels in childhood and increased occurrence of subclinical atherosclerosis in adulthood," said one of the JCEM study's authors, Markus Juonala, MD, PhD, of the University of Turku Finland. "The association was independent of conventional cardiovascular risk factors including serum lipids, blood pressure, smoking, diet, physical activity, obesity indices and socioeconomic status."
This study analyzed 2,148 subjects from the Cardiovascular Risk in Young Finns Study, aged 3-18 years at baseline. Subjects were re-examined at age 30-45 years. Childhood levels of vitamin D were measured from stored serum. Carotid IMT was measured on the posterior wall of the left carotid artery using ultrasound technology. Study subjects with 25-OH vitamin D levels in the lowest quartile in childhood had a significantly higher prevalence of high-risk IMT as adults (21.9% vs. 12.7%).
"More research is needed to investigate whether low vitamin D levels have a causal role in the development increased carotid artery thickness," Juonala said. "Nevertheless, our observations highlight the importance of providing children with a diet that includes sufficient vitamin D."
Low vitamin D predicts more severe strokes, poor health post-stroke
Stroke patients with low vitamin D levels were found to be more likely than those with normal vitamin D levels to suffer severe strokes and have poor health months after stroke, according to research presented at the American Stroke Association's International Stroke Conference 2015.
Low vitamin D has been associated in past studies with neurovascular injury (damage to the major blood vessels supplying the brain, brainstem, and upper spinal cord).
"Many of the people we consider at high risk for developing stroke have low vitamin D levels. Understanding the link between stroke severity and vitamin D status will help us determine if we should treat vitamin D deficiency in these high-risk patients," said Nils Henninger, M.D., senior study author and assistant professor of neurology and psychiatry at University of Massachusetts Medical School in Worchester.
Henninger and colleagues studied whether low blood levels of 25-hydroxyvitamin D, a marker of vitamin D status, is predictive of ischemic stroke severity and poor health after stroke in 96 stroke patients treated between January 2013 and January 2014 at a U.S. hospital.
• Overall, patients who had low vitamin D levels -defined as less than 30 nanograms per milliliter (ng/mL) - had about two-times larger areas of dead tissue resulting from obstruction of the blood supply compared to patients with normal vitamin D levels.
• This association was similar among patients who suffered lacunar strokes (in which the small, intricate arteries of the brain are affected) and patients with non-lacunar strokes (such as those caused by carotid disease or by a clot that originated elsewhere in the body).
• For each 10 ng/mL reduction in vitamin D level, the chance for healthy recovery in the three months following stroke decreased by almost half, regardless of the patient's age or initial stroke severity.
"It's too early to draw firm conclusions from our small study, and patients should discuss the need for vitamin D supplementation with their physician," Henninger said. "However, the results do provide the impetus for further rigorous investigations into the association of vitamin D status and stroke severity. If our findings are replicated, the next logical step may be to test whether supplementation can protect patients at high risk for stroke."
Limitations of the study include that most of the participants were Caucasian and the results might not fully translate to other ethnic groups.
Link between vitamin D deficiency and hypertension
New genetic research provides compelling evidence that low levels of vitamin D have a causal role in the development of high blood pressure (hypertension). The findings, published in The Lancet Diabetes & Endocrinology, suggest that vitamin D supplementation could be effective in combating some cases of hypertension.
"In view of the costs and side effects associated with antihypertensive drugs, the potential to prevent or reduce blood pressure and therefore the risk of hypertension with vitamin D is very attractive", explains study leader Professor Elina Hyppönen from the University of South Australia.
There has been considerable interest in the role of vitamin D in hypertension, but until now, a direct causal link has not been shown. Results from observational studies have suggested a strong association between low vitamin D levels and increases in blood pressure and hypertension, but randomised trials have not provided consistent evidence.
This Mendelian randomisation study used genetic data from the D-CarDia collaboration, involving over 146 500 individuals of European ancestry from across Europe and North America.
Researchers used two common genetic variants that affect circulating 25-hydroxyvitamin D or 25(OH)D concentrations (which are generally used to determine a person's vitamin D status), to measure the causal effect between vitamin D status and blood pressure and hypertension risk. They found that for each 10% increase in 25(OH)D concentration there was a drop in diastolic blood pressure (-0.29 mm Hg) and systolic blood pressure (-0.37 mm Hg), and an 8.1% decrease in the odds of developing hypertension.
According to Professor Hyppönen, "Mendelian randomisation helps to determine cause and effect because by using genetic data we can better avoid confounding, reverse causation, and bias. However, because we cannot exclude the possibility that our findings were caused by chance, they need to be replicated in an independent, similarly powered study. Further studies using randomised controlled trials are also needed to confirm causality and the potential clinical benefits of vitamin D supplementation."*
Writing in a linked Comment, Dr Shoaib Afzal and Dr Børge Nordestgaard from Copenhagen University Hospital and the University of Copenhagen in Denmark say, "Although [this] study is an important step towards delineation of the role of low vitamin D concentrations in the pathogenesis of hypertension, much remains unknown. Confirmation of these results in independent, similarly powered studies will be necessary, as will evidence of a corresponding benefit for the prevention of diseases caused by hypertension such as stroke. Finally, randomised intervention trials will be needed to determine whether vitamin D supplementation can be used to prevent or treat hypertension before such a strategy can be used clinically."
Sun lowers blood pressure
Exposing skin to sunlight may help to reduceblood pressure and thus cut the risk of heart attack and stroke, a study published in the Journal of Investigative Dermatology suggests.
Research carried out at the Universities of Southampton and Edinburgh shows that sunlight alters levels of the small messenger molecule, nitric oxide (NO) in the skin and blood, reducing blood pressure.
Martin Feelisch, Professor of Experimental Medicine and Integrative Biology at the University of Southampton, comments: "NO along with its breakdown products, known to be abundant in skin, is involved in the regulation of blood pressure. When exposed to sunlight, small amounts of NO are transferred from the skin to the circulation, lowering blood vessel tone; as blood pressure drops, so does the risk of heart attack and stroke."
While limiting sunlight exposure is important to prevent skin cancer, the authors of the study, including Dr Richard Weller of the University of Edinburgh, suggest that minimising exposure may be disadvantageous by increasing the risk of prevalent conditions related to cardiovascular disease.
Cardiovascular disease, often associated with high blood pressure, accounts for 30 per cent of deaths globally each year. Blood pressure and cardiovascular disease are known to vary according to season and latitude, with higher levels observed in winter and in countries further from the equator, where ultraviolet radiation from the sun is lower.
During the study, the skin of 24 healthy individuals was exposed to ultraviolet (UVA) light from tanning lamps for two sessions of 20 minutes each. In one session, the volunteers were exposed to both the UVA rays and the heat of the lamps. In another, the UV rays were blocked so that only the heat of the lamps affected the skin.
The results suggest that UVA exposure dilates blood vessels, significantly lowers blood pressure, and alters NO metabolite levels in the circulation, without changing vitamin D levels. Further experiments indicate that pre-formed stores of NO in the upper skin layers are involved in mediating these effects. The data are consistent with the seasonal variation of blood pressure and cardiovascular risk at temperate latitudes.
Professor Feelisch adds: "These results are significant to the ongoing debate about potential health benefits of sunlight and the role of Vitamin D in this process. It may be an opportune time to reassess the risks and benefits of sunlight for human health and to take a fresh look at current public health advice. Avoiding excess sunlight exposure is critical to prevent skin cancer, but not being exposed to it at all, out of fear or as a result of a certain lifestyle, could increase the risk of cardiovascular disease. Perhaps with the exception of bone health, the effects of oral vitamin D supplementation have been disappointing.
"We believe that NO from the skin is an important, so far overlooked contributor to cardiovascular health. In future studies we intend to test whether the effects hold true in a more chronic setting and identify new nutritional strategies targeted at maximizing the skin's ability to store NO and deliver it to the circulation more efficiently."
Low vitamin D blood levels = greater risk of heart disease in whites and Chinese, but not in blacks and Hispanics
Low vitamin D blood levels are linked to greater risk of heart disease in whites and Chinese, but not in blacks and Hispanics, according to a study appearing July, 2013 in JAMA, a journal published by the American Medical Association.
Growing evidence has suggested that low blood levels of 25-hydroxyvitamin are associated with higher risk of developing coronary heart disease among whites. Few of these studies included substantial numbers of people from other races.
Vitamin D levels tend to be lower among people from other racial and ethnic minority groups, and some of these populations have higher rates of heart disease. However, after correcting for other risk factors for heart disease in their large, multi-ethnic study group, the researchers reporting in the JAMA paper did not find an association between low vitamin D and cardiovascular events in their black and Hispanic study participants.
"Our study suggests that the results of ongoing vitamin D clinical trials conducted in white populations should be applied cautiously to people of other racial and ethnic backgrounds," said Cassianne Robinson-Cohen, the lead author for the JAMA paper. The senior author is Ian deBoer, University of Washington assistant professor of medicine, Division of Nephrology.
Robinson-Cohen is an affiliate instructor in epidemiology at the UW School of Public Health and a researcher at the Kidney Research Institute, where her team explores the genetic, metabolic and epidemiological factors related to heart and kidney disease.
She noted that the findings in their recent JAMA paper came from an observational study, not a randomized clinical trial, and could not guarantee cause and effect.
"Our future studies will examine the genetics affecting the levels and use of Vitamin D in the body to try to figure out why the link between low vitamin D blood levels and heart disease varies by race and ethnicity," she said. "We don't know for sure, but perhaps genes affecting the need for and use of vitamin D could have evolved to adapt to different levels of sun exposure in places where various ethnic subgroups of people originated."
Her team plans to look for variations in genes known to mediate Vitamin D activation and metabolism. She said these genes have been identified, but at present scientists haven't determined how gene variation influences susceptibility to the adverse effects of low vitamin D.
The report was from one of the projects within the Multi-Ethnic Study of Atherosclerosis. MESA is a major, long-term medical research effort sponsored by the National Heart Lung and Blood Institute of the National Institutes of Health. More than 6,800 men and women from six regions across the United States are participating in MESA. They were a diverse study group that was 38 percent white, 28 percent black, 22 percent Hispanic, and 12 percent Chinese. Robinson-Cohen and her team studied 6,436 MESA participants who enrolled between July 2000 and September 2002.
All participants were free of any known cardiovascular diseases at the time they enrolled, and had their blood levels of V25-hydroxyvitamin D measured. The mean age of participants at the start of the study was 62 (range 45 to 84 years) and slightly more than half were women.
The mean blood concentrations for whites was 30.1 ng/ml, Chinese 26.7, Hispanic 24.6, and blacks 19.2, The researchers tested the association of Vitamin D levels with the first incidence of coronary heart disease events – myocardial infarction, angina, cardiac arrest, or death from coronary heart disease — occurring from the start of the study until May 2012. During the eight-and-a-half year study, 361 participants had such an event. The researchers used several statistical risk analyses to check to see if links between blood vitamin D levels and coronary heart disease differed among white, black, Chinese and Hispanic populations.
"The differences in associations across race-ethnicity groups were consistent for both a broad and restricted definition of coronary heart disease and persisted after adjustment for known risk factors for coronary heart disease," the researchers noted in their paper.
Robinson-Cohen believes the strengths of the study are its size, duration, the use of several statistical analyses, the rigorous definition of heart disease events, and the efforts made to control for many confounding risk factors, such as age, gender, smoking, diabetes, blood pressure, cholesterol levels, physical activity, kidney disease,C-reactive protein concentrations, educational attainment, income and so on. A main weakness of the study, she said, is that it is observational, and therefore can't be ascertain cause and effect.
"To determine cause and effect, a large, multiethnic, randomized control clinical trial would need to be conducted," she said.
Robinson-Cohen pointed out, that beyond these specific results, the nature of the findings show the importance of designing medical research that includes a diverse ethnic and racial makeup of participants. Such multi-ethnic studies would help prevent cases where findings from one group are incorrectly applied to other groups.
"We need to make a bigger effort to design and fund medical studies with large enough representation of various racial and ethnic backgrounds that we don't draw ungrounded conclusions based on one group," Robinson-Cohen said.
Calcium and vitamin D improve cholesterol in postmenopausal women
Calcium and vitamin D supplements after menopause can improve women's cholesterol profiles. And much of that effect is tied to raising vitamin D levels, finds a new study from the Women's Health Initiative (WHI) published in Menopause, the journal of The North American Menopause Society (NAMS).
Whether calcium or vitamin D can indeed improve cholesterol levels has been debated. And studies of women taking the combination could not separate the effects of calcium from those of vitamin D on cholesterol. But this study is helping to settle those questions because it looked both at how a calcium and vitamin D supplement changed cholesterol levels and how it affected blood levels of vitamin D in postmenopausal women.
Daily, the women in the trial took either a supplement containing 1,000 mg of calcium and 400 IU of vitamin D3 or a placebo. The women who took the supplement were more than twice as likely to have vitamin D levels of at least 30 ng/mL (normal according to the Institute of Medicine) as were the women who took the placebo. Supplement users also had low-density lipoprotein (LDL—the "bad" cholesterol) levels that were between 4 and 5 points lower. The investigators discovered, in addition, that among supplement users, those with higher blood levels of vitamin D had higher levels of high-density lipoprotein (HDL—the "good" cholesterol) and lower levels of triglycerides (although for triglycerides to be lower, blood levels of vitamin D had to reach a threshold of about 15 ng/mL).
Taking the calcium and vitamin D supplements was especially helpful in raising vitamin D levels in women who were older, women who had a low intake, and women who had levels first measured in the winter—what you might expect. But lifestyle also made a difference. The supplements also did more to raise vitamin D levels in women who did not smoke and who drank less alcohol.
Vitamin D deficiency increases risk of heart disease
New research from the University of Copenhagen and Copenhagen University Hospital shows that low levels of vitamin D are associated with a markedly higher risk of heart attack and early death. The study involved more than 10,000 Danes and has been published in the well-reputed American journal Arteriosclerosis, Thrombosis and Vascular Biology.
Vitamin D deficiency has traditionally been linked with poor bone health. However, the results from several population studies indicate that a low level of this important vitamin may also be linked to a higher risk of ischemic heart disease, a designation that covers heart attack, coronary arteriosclerosis and angina. Other studies show that vitamin D deficiency may increase blood pressure, and it is well known that high blood pressure increases the risk of heart attack.
"We have now examined the association between a low level of vitamin D and ischemic heart disease and death in the largest study to date. We observed that low levels of vitamin D compared to optimal levels are linked to 40% higher risk of ischemic heart disease, 64% higher risk of heart attack, 57% higher risk of early death, and to no less than 81% higher risk of death from heart disease," says Dr. Peter Brøndum-Jacobsen, Clinical Biochemical Department, Copenhagen University Hospital.
The scientists have compared the 5% lowest levels of vitamin D (less than 15 nanomol vitamin per litre serum) with the 50% highest levels (more than 50 nanomol vitamin per litre serum). In Denmark, it is currently recommended to have a vitamin D status of at least 50 nanomol vitamin per litre serum.
The higher risks are visible, even after adjustment for several factors that can influence the level of vitamin D and the risk of disease and death. This is one of the methods scientists use to avoid bias.
Blood samples from more than 10,000 Danes
The population study that forms the basis for this scientific investigation is the Copenhagen City Heart Study, where levels of vitamin D were measured in blood samples from 1981-1983. Participants were then followed in the nationwide Danish registries up to the present.
"With this type of population study, we are unable to say anything definitive about a possible causal relationship. But we can ascertain that there is a strong statistical correlation between a low level of vitamin D and high risk of heart disease and early death. The explanation may be that a low level of vitamin D directly leads to heart disease and death. However, it is also possible that vitamin deficiency is a marker for poor health generally," says Børge Nordestgaard, clinical professor at the Faculty of Health and Medical Sciences, University of Copenhagen and senior physician at Copenhagen University Hospital.
Long-term goal is prevention
The scientists are now working to determine whether the connection between a low level of vitamin D and the risk of heart disease is a genuine causal relationship.
If this is the case, it will potentially have a massive influence on the health of the world population. Heart disease is the most common cause of adult death in the world according to the World Health Organization (WHO), which estimates that at least 17 million people die every year from heart disease.
"The cheapest and easiest way to get enough vitamin D is to let the sun shine on your skin at regular intervals. There is plenty of evidence that sunshine is good, but it is also important to avoid getting sunburned, which increases the risk of skin cancer. Diet with a good supply of vitamin D is also good, but it has not been proven that vitamin D as a dietary supplement prevents heart disease and death," says Børge Nordestgaard.
Vitamin D may help reduce heart risk in African-Americans
Supplementation of 60,000 IU monthly improves vascular function
In recent years supplementation with Vitamin D has been shown to reduce the risk of cardiovascular disease (CVD) in people who are deficient in the vitamin. Now new research from the Georgia Prevention Institute at Georgia Health Sciences University in Augusta indicates that supplementation with the "sunshine vitamin" may be particularly beneficial for overweight African-American adults, a population at increased risk for both CVD and Vitamin D deficiency.
According to Ryan A. Harris, PhD, assistant professor, the Georgia team's research suggests that Vitamin D supplementation cut the cardiovascular risk by improving the health and function of vascular endothelial cells, cells that line the inside of blood vessels. He will discuss the team's findings at the Experimental Biology 2011 meeting (EB 2011), being held April 9-13, 2011 at the Walter E. Washington Convention Center in Washington, DC. The presentation is entitled "Vitamin D Improves Flow-Mediated Dilation in African American Adults."
A Population at Risk
African-Americans as a group have multiple risk factors for CVD. They are more likely than people of other races to develop type 2 diabetes, a known contributor to CVD, and when they develop high blood pressure it tends to be more severe than that of other groups. African-Americans also have a greater risk of developing Vitamin D deficiency: The pigmentation in their skin inhibits their skin cells' ability to produce Vitamin D in response to exposure to sunlight.
In the study, 45 overweight African-American adults who were separated into two groups. (Overweight participants were chosen because carrying extra weight has been linked to inflammation in blood vessels, another risk for CVD.) One group, the treatment group, received 60,000 IU of Vitamin D in a single dose every 4 weeks for 16 weeks. The second group, the placebo group, received dummy pills. Although 60,000 IU seems like a high dose, Vitamin D has a half life of approximately 3 weeks, which means that half the dose is still in the body 3 weeks after it is taken. Given the time it takes the body to clear Vitamin D, a dose of 60,000 IU equals about 2,000 IU a day.
"We could have used daily dosing, but we knew compliance would be better with monthly dosing. One dose a month is easier than taking two pills a day," says Dr. Harris. He notes that participants reported no side effects.
At the beginning of the study, the researchers used an inflatable cuff to increase blood flow in the brachial arteries of the participants' arms, then used ultrasound to measure the arteries flow-mediated dilation. Flow-mediated dilation occurs when blood vessels dilate, or open up, in response to increased blood flow, which allows the blood to flow more freely. Vascular endothelial cells play a role in blood vessel dilation; endothelial cell dysfunction is considered to be the first sign of atherosclerosis, or "hardening of the arteries." When there is endothelial dysfunction, the blood vessels do not dilate as much and the heart has to pump harder to push blood through the vessels.
After 16 weeks, the researchers measured the participants' flow-mediated dilation again and found that flow-mediated dilation had improved in the treatment group, but not in the placebo group.
"This points to a beneficial effect of Vitamin D supplementation on endothelial cell function," says Dr. Harris. He adds that this is good news for African-Americans, given their risks for CVD. "If you're deficient in Vitamin D and you take supplements, you have a good probability of increasing endothelial function and therefore decreasing the risk of cardiovascular disease."
Exactly how Vitamin D works on the endothelial cells is the "million-dollar question" Dr. Harris says. "Vitamin D interacts with a lot of different systems in the body. It may decrease inflammation, which is better for endothelial function."
Vitamin D deficit doubles risk of stroke in whites, but not in blacks
Low levels of vitamin D, the essential nutrient obtained from milk, fortified cereals and exposure to sunlight, doubles the risk of stroke in whites, but not in blacks, according to a new report by researchers at Johns Hopkins.
Stroke is the nation's third leading cause of death, killing more than 140,000 Americans annually and temporarily or permanently disabling over half a million when there is a loss of blood flow to the brain.
Researchers say their findings, presented Nov. 15, 2010 at the American Heart Association's (AHA) annual Scientific Sessions in Chicago, back up evidence from earlier work at Johns Hopkins linking vitamin D deficiency to higher rates of death, heart disease and peripheral artery disease in adults.
The Hopkins team says its results fail to explain why African Americans, who are more likely to be vitamin D deficient due to their darker skin pigmentation's ability to block the sun's rays, also suffer from higher rates of stroke. Of the 176 study participants known to have died from stroke within a 14-year period, 116 were white and 60 were black. Still, African Americans had a 65 percent greater likelihood of suffering such a severe bleeding in or interruption of blood flow to the brain than whites, when age, other risk factors for stroke, and vitamin D deficiency were factored into their analysis.
"Higher numbers for hypertension and diabetes definitely explain some of the excess risk for stroke in blacks compared to whites, but not this much risk," says study co-lead investigator and preventive cardiologist Erin Michos, M.D., M.H.S., an assistant professor at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute. "Something else is surely behind this problem. However, don't blame vitamin D deficits for the higher number of strokes in blacks."
Nearly 8,000 initially healthy men and women of both races were involved in the latest analysis, part of a larger, ongoing national health survey, in which the researchers compared the risk of death from stroke between those with the lowest blood levels of vitamin D to those with higher amounts. Among them, 6.6 percent of whites and 32.3 percent of blacks had severely low blood levels of vitamin D, which the experts say is less than 15 nanograms per milliliter.
"It may be that blacks have adapted over the generations to vitamin D deficiency, so we are not going to see any compounding effects with stroke," says Michos, who notes that African Americans have adapted elsewhere to low levels of the bone-strengthening vitamin, with fewer incidents of bone fracture and greater overall bone density than seen in Caucasians.
"In blacks, we may not need to raise vitamin D levels to the same level as in whites to minimize their risk of stroke" says Michos, who emphasizes that clinical trials are needed to verify that supplements actually do prevent heart attacks and stroke. In her practice, she says, she monitors her patients' levels of the key nutrient as part of routine blood work while also testing for other known risk factors for heart disease and stroke, including blood pressure, glucose and lipid levels.
Michos cautions that the number of fatal strokes recorded in blacks may not have been statistically sufficient to find a relationship with vitamin D deficits. And she points out that the study only assessed information on deaths from stroke, not the more common "brain incidents" of stroke, which are usually non-fatal, or even mini-strokes, whose symptoms typically dissipate in a day or so. She says the team's next steps will be to evaluate cognitive brain function as well as non-fatal and transient strokes and any possible tie-ins to nutrient deficiency.
Besides helping to keep bones healthy, vitamin D plays an essential role in preventing abnormal cell growth, and in bolstering the body's immune system. The hormone-like nutrient also controls blood levels of calcium and phosphorus, essential chemicals in the body. Shortages of vitamin D have also been tied to increased rates of breast cancer and depression in the elderly.
Michos recommends that people maintain good vitamin D levels by eating diets rich in such fish as salmon and tuna, consuming vitamin-D fortified dairy products, and taking vitamin D supplements. She also promotes brief exposure daily to the sun's vitamin D-producing ultraviolet light. And to those concerned about the cancer risks linked to too much time spent in the sun, she says as little as 10 to 15 minutes of daily exposure is enough during the summer months.
If vitamin supplements are used, Michos says that daily doses between 1,000 and 2,000 international units are generally safe and beneficial for most people, but that people with the severe vitamin D deficits may need higher doses under close supervision by their physician to avoid possible risk of toxicity.
The U.S. Institute of Medicine (IOM) previously suggested that an adequate daily intake of vitamin D is between 200 and 600 international units. However, Michos argues that this may be woefully inadequate for most people to raise their vitamin D blood levels to a healthy 30 nanograms per milliliter. The IOM has set up an expert panel to review its vitamin D guidelines, with new recommendations expected by the end of the year. Previous results from the same nationwide survey showed that 41 percent of men and 53 percent of women have unhealthy amounts of vitamin D, with nutrient levels below 28 nanograms per milliliter.
Vitamin D Levels Linked With Health of Blood Vessels
A lack of vitamin D, even in generally healthy people, is linked with stiffer arteries and an inability of blood vessels to relax, research from the Emory/Georgia Tech Predictive Health Institute has found.
The results add to evidence that lack of vitamin D can lead to impaired vascular health, contributing to high blood pressure and the risk of cardiovascular disease. Study participants who increased their vitamin D levels were able to improve vascular health and lower their blood pressure.
The data was presented by Ibhar Al Mheid, MD, a cardiovascular researcher at Emory University School of Medicine, at the annual American College of Cardiology meeting in New Orleans. Al Mheid is one of five finalists for the ACC's Young Investigators Award competition in physiology, pharmacology and pathology. He is working with Arshed Quyyumi, MD, professor of medicine and director of the Emory Cardiovascular Research Institute.
The 554 participants in the study were Emory or Georgia Tech employees -average age 47 and generally healthy -- who are taking part in the Center for Health Discovery and Well Being, part of the Emory/Georgia Tech Predictive Health Institute.
The average level of 25-hydroxyvitamin D (a stable form of the vitamin reflecting diet as well as production in the skin) in participants' blood was 31.8 nanograms per milliliter. In this group, 14 percent had 25-hydroxyvitamin D levels considered deficient, or less than 20 nanograms per milliliter, and 33 percent had levels considered insufficient, less than 30 nanograms per milliliter.
The researchers monitored the ability of participants' blood vessels to relax by inflating and then removing a blood pressure cuff on their arms. To allow blood to flow back into the arm, blood vessels must relax and enlarge -- a change that can be measured by ultrasound. The researchers also made other measurements of smaller blood vessels and examined the resistance to blood flow imposed by the arteries.
Even after controlling for factors such as age, weight and cholesterol, people with lower vitamin D levels still had stiffer arteries and impaired vascular function, Al Mheid says.
"We found that people with vitamin D deficiency had vascular dysfunction comparable to those with diabetes or hypertension," he says.
Throughout the body, a layer of endothelial cells lines the blood vessels, controlling whether the blood vessels constrict or relax and helping to prevent clots that lead to strokes and heart attacks.
"There is already a lot known about how vitamin D could be acting here," Al Mheid says. "It could be strengthening endothelial cells and the muscles surrounding the blood vessels. It could also be reducing the level of angiotensin, a hormone that drives increased blood pressure, or regulating inflammation."
Most Americans generally get the majority of their vitamin D from exposure to sunlight or from dietary supplements; fortified foods such as milk or cereals are a minor source. A few foods, such as oily fish, naturally contain substantial amounts of vitamin D.
Participants whose vitamin D levels increased over the next six months, either from dietary supplements or ample sun exposure, tended to improve their measures of vascular health and had lower blood pressure. Forty-two study participants with vitamin D insufficiency whose levels later went back to normal had an average drop in blood pressure of 4.6 millimeters mercury.
Vitamin D prevents clogged arteries in diabetics
People with diabetes often develop clogged arteries that cause heart disease, and new research at Washington University School of Medicine in St. Louis suggests that low vitamin D levels are to blame.
In a study published Nov. 9, 2012 in the Journal of Biological Chemistry, the researchers report that blood vessels are less like to clog in people with diabetes who get adequate vitamin D. But in patients with insufficient vitamin D, immune cells bind to blood vessels near the heart, then trap cholesterol to block those blood vessels.
“About 26 million Americans now have type 2 diabetes,” says principal investigator Carlos Bernal-Mizrachi, MD. “And as obesity rates rise, we expect even more people will develop diabetes. Those patients are more likely to experience heart problems due to an increase in vascular inflammation, so we have been investigating why this occurs.”
In earlier research, Bernal-Mizrachi, an assistant professor of medicine and of cell biology and physiology, and his colleagues found that vitamin D appears to play a key role in heart disease. This new study takes their work a step further, suggesting that when vitamin D levels are low, a particular class of white blood cell is more likely to adhere to cells in the walls of blood vessels.
Vitamin D conspires with immune cells called macrophages either to keep arteries clear or to clog them. The macrophages begin their existence as white blood cells called monocytes that circulate in the bloodstream. But when monocytes encounter inflammation, they are transformed into macrophages, which no longer circulate.
In the new study, researchers looked at vitamin D levels in 43 people with type 2 diabetes and in 25 others who were similar in age, sex and body weight but didn’t have diabetes.
They found that in diabetes patients with low vitamin D — less than 30 nanograms per milliliter of blood — the macrophage cells were more likely to adhere to the walls of blood vessels, which triggers cells to get loaded with cholesterol, eventually causing the vessels to stiffen and block blood flow.
“We took everything into account,” says first author Amy E. Riek, MD, instructor in medicine. “We looked at blood pressure, cholesterol, diabetes control, body weight and race. But only vitamin D levels correlated to whether these cells stuck to the blood vessel wall.”
Riek and Bernal-Mizrachi say what’s not yet clear is whether giving vitamin D to people with diabetes will reverse their risk of developing clogged arteries, a condition called atherosclerosis. They now are treating mice with vitamin D to see whether it can prevent monocytes from adhering to the walls of blood vessels near the heart, and they also are conducting two clinical trials in patients.
In one of those studies, the researchers are giving vitamin D to people with diabetes and hypertension to see whether the treatment may lower blood pressure. In the second study, African Americans with type 2 diabetes are getting vitamin D along with their other daily medications, and the research team is evaluating whether vitamin D supplements can slow or reverse the progression of heart disease.
Sometime in the next several months, the scientists hope to determine whether vitamin D treatment can reverse some of the risk factors associated with cardiovascular disease.
“In the future, we hope to generate medications, potentially even vitamin D itself, that help prevent the deposit of cholesterol in the blood vessels,” Bernal-Mizrachi explains. “Previous studies have linked vitamin D deficiency in these patients to increases in cardiovascular disease and in mortality. Other work has suggested that vitamin D may improve insulin release from the pancreas and insulin sensitivity. Our ultimate goal is to intervene in people with diabetes and to see whether vitamin D might decrease inflammation, reduce blood pressure and lessen the likelihood that they will develop atherosclerosis or other vascular complications.”
Studies find treating vitamin D deficiency significantly reduces heart disease risk
Preventing and treating heart disease in some patients could be as simple as supplementing their diet with extra vitamin D, according to two new studies
Preventing and treating heart disease in some patients could be as simple as supplementing their diet with extra vitamin D, according to two new studies at the Intermountain Medical Center Heart Institute in Murray, Utah.
Researchers at the Intermountain Medical Center Heart Institute last fall demonstrated the link between vitamin D deficiency and increased risk for coronary artery disease. These new studies show that treating vitamin D deficiency with supplements may help to prevent or reduce a person's risk for cardiovascular disease and a host of other chronic conditions. They also establish what level of vitamin D further enhances that risk reduction.
"Vitamin D replacement therapy has long been associated with reducing the risk of fractures and diseases of the bone," says Dr. J. Brent Muhlestein, MD, director of cardiovascular research at the Intermountain Medical Center Heart Institute. "But our findings show that vitamin D could have far greater implications in the treatment and reduction of cardiovascular disease and other chronic conditions than we previously thought."
For the first study, researchers followed two groups of patients for an average of one year each. In the first study group, over 9,400 patients, mostly female, reported low initial vitamin D levels, and had at least one follow up exam during that time period. Researchers found that 47 percent of the patients who increased their levels of vitamin D between the two visits showed a reduced risk for cardiovascular disease.
In the second study, researchers placed over 31,000 patients into three categories based on their levels of vitamin D. The patients in each category who increased their vitamin D levels to 43 nanograms per milliliter of blood or higher had lower rates of death, diabetes, cardiovascular disease, myocardial infarction, heart failure, high blood pressure, depression, and kidney failure. Currently, a level of 30 nanograms per milliliter is considered "normal."
Heidi May, PhD, a cardiovascular clinical epidemiologist with the Intermountain Medical Center Heart Institute, and one of the study's authors, says the link between low levels of vitamin D and increased risk for a variety of diseases is significant.
"It was very important to discover that the 'normal' levels are too low. Giving physicians a higher level to look for gives them one more tool in identifying patients at-risk and offering them better treatment," says Dr. May.
Dr. Muhlestein says the results of these studies will change the way he treats his patients.
"Although randomized trials would be useful and are coming, I feel there is enough information here for me to start treatment based on these findings," he says.
Treatment options in this case are simple, starting with a blood test to determine a patient's vitamin D level. If low levels are detected, supplements and/or increased exposure to sunlight may be prescribed.
Increasing vitamin D intake by 1000 to 5000 international units (IU) a day may be appropriate, depending on a patient's health and genetic risk, says Dr. Muhlestein. He says supplements are the best source of vitamin D because they are relatively inexpensive and can be found at almost any supermarket or drug store. Most supplements provide an average of 400 IU per tablet.
More severe heart disease found in patients with vitamin D deficiency
Vitamin D deficiency is an independent risk factor for heart disease with lower levels of vitamin D being associated with a higher presence and severity of coronary artery disease, according to research to be presented at the American College of Cardiology's 63rd Annual Scientific Session.
A growing body of research shows that vitamin D may be beneficial in preventing heart disease. Several recent studies also support the idea that low levels of vitamin D are linked to an increased risk of heart disease; however, it is still not clear whether adding vitamin D supplements may help reduce that risk.
In the largest study of its kind to evaluate the relationship between vitamin D levels and coronary artery disease, vitamin D deficiency (20ng/mL) was observed in 70.4 percent of patients undergoing coronary angiography – an imaging test used to see how blood flows through the arteries in the heart. Vitamin D deficiency was associated with higher prevalence of coronary artery disease, with a 32 percent higher occurrence in patients with the lowest vitamin D levels and a near 20 percent higher frequency of severe disease affecting multiple vessels. A progressive increase in heart disease was found according to the severity of vitamin D deficiency. Patients with values lower than 10 mg/dl had a near two-fold increased rate of coronary atherosclerosis as compared with those showing normal levels.
Researchers evaluated vitamin D levels in 1,484 patients. Vitamin D deficiency was defined as levels lower than 20ng/mL, and severe vitamin D deficiency was defined as levels under 10ng/mL. Patients were considered to have coronary artery disease if they had a diameter reduction of greater than 50 percent in at least one coronary artery. The extent and severity of heart disease were measured by quantitative coronary angiography – a procedure that determines the degree of blockage in arteries.
"Present results suggest vitamin D deficiency to be the cause rather than the consequence of atherosclerosis," said Monica Verdoia, M.D., specializing cardiologist at the Department of Cardiology, Ospedale Maggiore della Carità, Eastern Piedmont University in Novara, Italy, and investigator on the study on behalf of the Novara Atherosclerosis study group by Prof. Giuseppe De Luca. "Although evidence of benefits with vitamin D supplementation in cardiovascular outcomes are still lacking, strategies to raise endogenous vitamin D should probably be advised in the prevention of cardiovascular disease."
A diet rich in vitamin D and moderate exercise outdoors should be advised in both patients with and without cardiovascular disease, Verdoia said. Vitamin D acts as a regulator on the function of the immune system as well as inflammatory processes that contribute to risk factors for heart disease, she said.
Verdoia said the importance of the study is to provide deeper insight into stratification tools for assessing the risk of coronary artery disease in a real world population, where vitamin D deficiency has a dramatic prevalence. She stresses the need to make funding a priority in the research on vitamin D in cardiovascular prevention. The research team plans to proceed with clinical trials evaluating the treatment of vitamin D deficiency and to investigate the mechanisms by which vitamin D can influence the development of atherosclerosis.
Researchers estimate that more than half of U.S. adults are vitamin D deficient, with the highest rates among African Americans and Hispanics. Vitamin D is being studied for its possible connection to several diseases and health problems, including diabetes, high blood pressure, multiple sclerosis, autoimmune conditions, bone disorders and some types of cancer.
A limitation of the study is that researchers did not evaluate the long-term outcomes for study patients, so it is unknown whether those with lower vitamin D levels experienced a higher rate of recurrent events or a quicker progression of the coronary disease, although other studies have suggested this is the case.
Vitamin D Can Help Prevent Hypertension
The world's largest study to examine the link between vitamin D levels and hypertension has found that low levels of Vitamin D can be a major cause of hypertension.
Researchers presented their findings at the 2013 conference of the European Society of Human Genetics (ESHG).
Data were gathered from 35 studies, which included more than 155,000 participants from different parts of Europe and North America.
Dr. Vimal Karani S, from the Institute of Child Health, University College London, London, UK, led the study.
Participants with high levels of 25-hydroxyvitamin D (25(OH)D) had reduced blood pressure and were at a lower risk of developing hypertension.
Dr. Vimal Karani S, said: "We knew from earlier observational studies that low 25(OH)D concentrations were likely to be associated with increases in blood pressure and hypertension, but correlation is not causality.
Additionally, randomized controlled trials of vitamin D supplementation in humans have produced inconsistent effects on cardiovascular outcomes. The whole picture was somewhat confused, and we decided to try to figure it out once and for all."
To measure the individuals' vitamin D status and test for an association with blood pressure, the researchers used genetic variations called single nucleotide polymorphisms, or SNPs as proxy markers.
For every 10% increase in 25(OH)D concentrations the researchers noted the risk of developing hypertension decreased by 8.1%.
Dr. Karani S., said that the approach they followed, called Mendelian randomization, allowed them to make accurate conclusions, "by using this approach we can determine the cause and effect and be pretty sure that we've come to the right conclusion on the subject."
The researchers said that Vitamin D deficiency is a very common problem in the Western world, particularly because obesity can cause Vitamin D deficiency and obesity levels are highest in Western countries, according to a study published in a recent issue of PLoS Medicine
People with high levels of vitamin D in their blood enjoy several benefits, apart from improved bone health. Researchers from Boston University School of Medicine reported in PLOS ONE that people with high levels of vitamin D have significantly better immunity and a reduced risk of several diseases.
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Dr. Karani said that the study provides further data to support the importance of vitamin D. It suggests that vitamin D supplements or food fortification can significantly reduce the risk of cardiovascular disease.
"We now intend to continue this work by examining the causal relationship between vitamin D status and other cardiovascular disease-related outcomes such as lipid-related phenotypes, for example,cholesterol, inflammatory markers such as C-reactive protein, and type 2 diabetes and markers of glucose metabolism.
We believe that we still have a lot to find out about the effect of Vitamin D deficiency on health, and we now know that we have the tools to do so."
Vitamin D supplements may help African Americans lower blood pressure
Vitamin D supplements significantly reduced blood pressure in the first large controlled study of African-Americans, researchers report in the American Heart Association journal Hypertension.
In the prospective trial, a three-month regimen of daily vitamin D increased circulating blood levels of vitamin D and resulted in a decrease in systolic blood pressure ranging from .7 to four mmHg (depending upon the dose given), compared with no change in participants who received a placebo.
Systolic blood pressure, the top and highest number in a reading, is pressure in the arteries when the heart beats. Diastolic blood pressure, the bottom and lower number, is pressure in the arteries between heart beats.
"Although this needs to be studied further, the greater prevalence of vitamin D deficiency among African-Americans may explain in part some of the racial disparity in blood pressure," said John P. Forman, M.D., M.Sc., lead author of the study and Assistant Professor of Medicine in the Renal Division and Kidney Clinical Research Institute at Brigham and Women's Hospital in Boston, Mass.
African-Americans have higher rates of hypertension and lower levels of circulating 25-hydroxyvitamin D (vitamin D3 or cholecalciferol) than the rest of the U.S. population. Few studies have included enough African-Americans to determine whether vitamin D supplements might reduce the racial disparity.
To explore this, researchers from seven major teaching hospitals conducted a four-arm, randomized, double-blinded study of 250 black adults. They tested blood pressure after a three-month regimen of daily vitamin D supplementation at one of three doses, and compared the findings with a group taking placebo vitamins:
Taking 1,000 units of vitamin D each day for three months was associated with a .7 mm Hg decrease in systolic blood pressure.
Taking 2,000 units was linked to a 3.4 mm Hg decrease.
Taking 4,000 units netted a 4 mm Hg drop.
Participants taking placebo supplements had an average increase of 1.7 mm Hg.
"The gains we saw were significant but modest," Forman said.
Furthermore, diastolic blood pressure didn't change in any of the four groups. In prospective studies, lower blood levels of 25-hydroxyvitamin D have been independently linked with an increased risk of developing hypertension.
"If vitamin D supplementation lowered blood pressure among African-Americans, its widespread use could have major public health benefits," said Andrew T. Chan, M.D., M.P.H., co-author of the study and Assistant Professor of Medicine in the Division of Gastroenterology at Massachusetts General Hospital.