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Vitamin-D-Deficiency Link to CHD

Jun 15, 2008 - 0 comments

Further Evidence Supports Vitamin-D-Deficiency Link to CHD  CME
June 11, 2008 — Further evidence that vitamin-D deficiency may increase the risk of heart disease has come from a new case-control study [1].

The study, published in the June 9, 2008 issue of the Archives of Internal Medicine, found that low levels of 25-dihydroxyvitamin-D (25[OH]D) were associated with a higher risk of myocardial infarction (MI) in a graded manner, even after researchers controlled for factors known to be associated with coronary artery disease.

The authors, led by Dr Edward Giovannucci (Harvard School of Public Health, Boston, MA), note that in most populations studied, the rate of cardiovascular death is elevated at higher latitudes, increases during the winter months, and is lower at high altitudes, a pattern consistent with an adverse effect of low levels of vitamin D, which are more prevalent at higher latitudes, during the winter, and at lower altitudes.

While alternative explanations for these observations are possible, they point out that a variety of plausible biological mechanisms support a role for vitamin D in heart disease. For example, the vitamin-D axis affects vascular smooth-muscle-cell proliferation, inflammation, vascular calcification, the renin-angiotensin system, and blood pressure.

To look at this issue further, they prospectively examined 25(OH)D concentrations in relation to risk of MI in a nested case-control study involving 18,225 men in the Health Professionals Follow-up Study (HPFS). The men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at baseline.

During 10 years of follow-up, 454 men developed nonfatal MI or fatal coronary heart disease (cases), and 900 controls were selected matched for age, date of blood collection, and smoking status.

Results showed that men deficient in 25(OH)D were found to be at increased risk for MI compared with those considered to be sufficient in 25(OH)D (> 30 ng/mL).

Giovannucci et al emphasize that men with circulating 25(OH)D levels of at least 30 ng/mL had approximately half the risk of MI, independent of other cardiovascular risk factors, and this association was suggestively stronger for fatal CHD, although the number of cases was too small to make definitive conclusions.

They note that only 23% of the men in the HPFS had levels of 25(OH)D of at least 30 ng/mL, which is typical of many populations, and the prevalence of deficiency is even higher in subpopulations such as dark-skinned individuals and elderly persons. In individuals in sun-rich environments, where clothing or cultural practices do not appreciably limit vitamin-D production, 25(OH)D levels of 54 to 90 ng/mL are attained, they report, adding that it is not possible from these data to evaluate whether levels greater than 35 ng/mL would be associated with an even greater MI risk reduction.

While vitamin-D supplementation was not shown to affect cardiovascular risk in the Women's Health Initiative, the authors point out that the range of vitamin-D levels was much narrower in that study, which would have made it more difficult to detect any effect. They say that to increase 25(OH)D levels from 12 to 35.5 ng/mL would require approximately 3000 IU of vitamin D daily, and although such intakes may seem high by current standards, increasing evidence demonstrates no toxic effects at intakes below 10,000 IU/day. Because current sources of vitamin D provide much less (eg, a glass of milk has approximately 100 IU), those who achieve high levels such as 35 ng/mL naturally do so largely through sun exposure, they add.

If the association seen in this study is causal, which remains to be established, the amount of vitamin D required for optimal benefit may be much higher than would be provided by current recommendations (200-600 IU/day), especially in those with minimal sun exposure, Giovannucci et al comment. Thus, the present findings add further support that the current dietary requirements of vitamin D need to be increased to have an effect large enough for potential health benefits, they conclude.

This study was supported by the National Cancer Institute and the National Heart, Lung, and Blood Institute. Two of the study authors have obtained funding. Another study author is a consultant for Diasorin Corp.


Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men. A prospective study. Arch Intern Med. 2008;168:1174-1180.

"Delipidated" HDL: A new option for plaque regression?

May 17, 2008 - 0 comments

"Delipidated" HDL: A new option for plaque regression?
Other studies have established that increasing pre-beta HDL increases cholesterol efflux and that pre-beta HDL is the most effective form of HDL for lipid removal from arterial plaque via reverse cholesterol transport. Plasma delipidation, through apheresis, converts alpha HDL to pre-beta HDL and in theory may lead to regression of atherosclerosis, something preclinical research has demonstrated in a rabbit model, Waksman explained. He likened pre-beta HDL to an "empty dump truck" with space to transport cholesterol out of arterial plaques, as opposed to the more prevalent alpha HDL, which functions more like a "full dump trunk." The delipidation process converts alpha HDL to pre-beta HDL.

Study conducted in ACS (Acute Coronary Syndrome in patients with CAD) patients
Waksman et al's study randomized 28 patients with ACS scheduled for cardiac catheterization to either HDL delipidation and reinfusion or undelipidated plasma reinfusion. The HDL apheresis/reinfusion ((apheresis: Greek: "to take away") is a medical technology in which the blood of a donor or patient is passed through an apparatus that separates out one particular constituent and returns the remainder to the circulation.)  procedure was repeated seven times, once per week, and IVUS was performed two weeks after the final procedure.

According to Waksman, the weekly lipid apheresis/reinfusion schedule was borrowed from the high-profile ApoA-1 Milano (ETC-216, Pfizer) study, which showed improvements on atherosclerotic burden following an infusion regimen of a recombinant HDL mimetic.

For the first part of the study, investigators confirmed that the apheresis procedure did indeed increase the proportion of pre-beta HDL (from about 5.6% in the sample to 92.8% in the sample) and reduced the proportion of alpha HDL (from about 92.8% of the sample to 20.9% in the sample). Associated with the increase in pre-beta HDL was a fivefold rise in cholesterol efflux seen in patients receiving the delipidated plasma vs the control group, they report. All reinfusion sessions were well tolerated, and there was no signal of an adverse biochemical or hemodynamic reaction to therapy.

Possible effects on atherosclerosis?

In exploratory IVUS analyses, reductions in total atheroma volume and in plaque burden were greater in the delipidation group, as compared with the control group, although the differences from baseline were not statistically significant—likely due to the small study size. Waksman called the observations "provocative," particularly since the changes were occurring over such a short period of time.

By way of comparison, he and his colleagues compared their IVUS findings with those of Nissen et al's study of recombinant apoA-1 Milano and found that the effects on atheroma volume were comparable between the two studies.
While a larger trial is necessary to confirm the results as well as determine the optimum number of repeats necessary for therapy, Waksman is cautiously optimistic about the findings. He explained that the aim of the therapy would be plaque stabilization, so that a patient, theoretically, would require the procedure only to "stabilize" their ACS.

But he points out that most of the patients in this study were already taking statins, so the changes seen in the plaques were on top of statin therapy. So far, he said, the strategy seems safe and would be a welcome addition in a field that has seen major disappointment in recent years. "The HDL story is not over," he said, "but there are not a lot of options left."

Discussing the study results after their presentation, Dr Peter Fitzgerald (Stanford School of Medicine, CA), whose core lab was one of two that conducted the blinded analysis of the IVUS data, suggested that the results were intriguing but that, given the sample size, would have to be "taken with a grain of salt."

Also commenting on the findings, Dr Roger Blumenthal (Johns Hopkins, Baltimore, MD) called the data "promising."
"This is very exciting and potentially much more useful than the work done by the Cleveland Clinic on apoA-1 Milano," he said. So far, he pointed out, apoA-1 Milano has not worked in clinical trials. "This technique by the Dr Waksman et al is very exciting and has great pilot data. I am looking forward to larger-scale trials on it. . . . This therapy clearly warrants more investigation."


Note: Remember the Italian Clan that did not get heart disease? The lipid component from these people was called apoA-1 Milano, and was synthasized for experimentation.

*IVUS= intravenous ultrasound= used during cardiac catheterization as a separate means of visualizing plaque formations (3D) in addition to angiography.

Daily Positive Affirmations

May 06, 2008 - 0 comments

Daily Positive Affirmations

I am openness, willing to show myself to others, ready to receive their confidences.
I use my courage and strength to take new risks and complete difficult tasks.

I gather the strength to open my eyes and see the sources of my mental confusion.

I am potential, committed to developing the talents and opportunities I have been given.

I am stability and movement, able to keep my balance in the midst of change and competing desires.

I am new emotional energy, I open myself to experience its depths, I give voice to my longings and desires.

I am a fruitful gardener, ready for harvest, created by hard work, discipline and organization.

Panic Attacks Linked To Heart Attack Risk In Women

May 06, 2008 - 5 comments

ScienceDaily (Oct. 2, 2007) — Older women who experience at least one full-blown panic attack may have an increased risk of having a heart attack or stroke and an increased risk of death in the next five years, according to a new report.

Panic attacks involve the sudden development of fear, anxiety or extreme discomfort accompanied by four or more additional symptoms, according to background information in the article. They may occur sporadically or as part of an anxiety disorder, such as panic disorder, social anxiety disorder or phobias.

Jordan W. Smoller, M.D., Sc.D., of Massachusetts General Hospital, Boston, and colleagues studied 3,369 healthy postmenopausal women (age 51 to 83, average age 65.9). When they entered the study between 1997 and 2000, the women filled out a questionnaire about the occurrence of panic attacks in the previous six months. They were then followed for an average of 5.3 years to see whether they had a heart attack or stroke or died from any cause.
About 10 percent of the women reported having a full-blown panic attack in the six months prior to the study. After the researchers adjusted for other cardiovascular risk factors, having one or more panic attacks was associated with four times the risk of myocardial infarction (heart attack), three times the risk of having a heart attack or stroke and nearly twice the risk of death from any cause. These associations remained after controlling for depression, suggesting that panic attacks may be a separate, independent risk factor for cardiovascular events.

The results add panic attacks to the list of emotions and psychiatric symptoms that have already been linked to cardiovascular risk, including depression, anger and hostility, the authors note. Panic attacks could be associated with other cardiovascular risk factors, such as hypertension. Alternatively, anxiety could contribute to adverse cardiovascular effects, such as coronary artery spasm, tendency toward increased blood clotting or disturbances in heart rhythm.

"These results suggest that panic anxiety is a marker for increased risk of cardiovascular morbidity and mortality among postmenopausal women," the authors conclude. "Future studies are needed to clarify the causal connection, if any, between panic attacks and cardiovascular events. Our results imply, however, that older women with a recent history of panic attacks represent a subgroup at elevated risk of myocardial infarction and stroke in whom careful monitoring and cardiovascular risk reduction may be particularly important."

This research is published in the October issue of Archives of General Psychiatry.
Reference: Arch Gen Psychiatry. 2007;64(10):1153-1160.

The Women's Health Initiative program is funded by the National Heart, Lung and Blood Institute, U.S. Department of Health and Human Services. The Myocardial Ischemia and Migraine Study was funded by Glaxo Wellcome (now GlaxoSmithKline).