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The Diet-Heart Hypothesis: Subdividing Lipoproteins Two posts ago, we made the rounds of the commonly measured blood lipids (total cholesterol, LDL, HDL, triglycerides) and how they associate with cardiac risk. It's important to keep in mind that many things associate with cardiac risk, not just blood lipids. For example, men with low serum vitamin D are at a 2.4-fold greater risk of heart attack than men with higher D levels. That alone is roughly equivalent to the predictive power of the blood lipids you get measured at the doctor's office. Coronary calcium scans (a measure of blood vessel calcification) also associate with cardiac risk better than the most commonly measured blood lipids. Lipoproteins Can be Subdivided into Several Subcategories In the continual search for better measures of cardiac risk, researchers in the 1980s decided to break down lipoprotein particles into sub-categories. One of these researchers is Dr. Ronald M. Krauss. Krauss published extensively on the association between lipoprotein size and cardiac risk, eventually concluding (source): The plasma lipoprotein profile accompanying a preponderance of small, dense LDL particles (specifically LDL-III) is associated with up to a threefold increase in the susceptibility of developing [coronary artery disease]. This has been demonstrated in case-control studies of myocardial infarction and angiographically documented coronary disease. Krauss found that small, dense LDL (sdLDL) doesn't travel alone: it typically comes along with low HDL and high triglycerides*. He called this combination of factors "lipoprotein pattern B"; its opposite is "lipoprotein pattern A": large, buoyant LDL, high HDL and low triglycerides. Incidentally, low HDL and high triglycerides are hallmarks of the metabolic syndrome, the quintessential modern metabolic disorder. Krauss and his colleagues went on to hypothesize that sdLDL promotes atherosclerosis because of its ability to penetrate the artery wall more easily

25-hydroxyvitamin D levels inversely associate with risk for developing coronary artery calcification. de Boer IH, Kestenbaum B, Shoben AB, Michos ED, Sarnak MJ, Siscovick DS. J Am Soc Nephrol. 2009 Aug;20(8):1805-12. Epub 2009 May 14. PMID: 19443637 doi: 10.1681/ASN.2008111157 "In conclusion, lower 25-hydroxyvitamin D concentrations associate with increased risk for incident CAC. Accelerated development of atherosclerosis may underlie, in part, the increased cardiovascular risk associated with vitamin D deficiency."

A recent Wall Street Journal article "Defending Against Disease -- With Vitamin D New Studies Suggest It Isn't Just Bones That Might Benefit" by the wonderful Melinda Beck highlights benefits of Vitamin D3. In TYP, we've known the benefits for years :) but it's nice to see the rest of the world catching up. The benefits of Vitamin D3 are potent, powerful immunomodulation -- to the point where autoimmune diseases, viral and bacterial infections and cancer are effectively reduced. What is the value for heart disease and diabetes prevention? In hemodialysis patients, great lessons are can be learned. Nephrologists often describe patients with severe (stage 5) chronic kidney disease (CKD) patients on hemodialysis as having 'hearts of stone, blood vessels of glass.' Unfortunately over 70% of chronic hemodialysis patients have coronary artery disease (and Lp(a)). What medical science shows is that Agatston coronary calcification scores can be dramatically reduced when vitamin D is replenished and calcium is restricted. Sevelamer (Renagel) is a calcium-free, metal-free polymer phosphate binder. In 52-weeks, calcium restriction, a phosphate-binder and vitamin D resulted in one individual in a 21% reduction in Agatston CAC score (from 968 to 756; see Figure 2).

What causes coronary heart disease or coronary atherosclerotic plaque, this thing that we track with heart scans? Well, here are a few little-publicized facts about heart disease that you are unlikely to hear from your When's-the-next-stent? cardiologist or the What is there besides statins? primary care doctor. (Since everybody knows that smoking is a modifiable risk for heart disease that can be readily identified, let's focus on the blood tests that reveal heart disease causes.)

Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography.\nPilz S, März W, Wellnitz B, Seelhorst U, Fahrleitner-Pammer A, Dimai HP, Boehm BO, Dobnig H.\nJ Clin Endocrinol Metab. 2008 Oct;93(10):3927-35. Epub 2008 Aug 5.\nPMID: 18682515

Low vitamin d levels predict stroke in patients referred to coronary angiography.\nPilz S, Dobnig H, Fischer JE, Wellnitz B, Seelhorst U, Boehm BO, März W.\nStroke. 2008 Sep;39(9):2611-3. Epub 2008 Jul 17.\nPMID: 18635847 \ndoi: 10.1161/STROKEAHA.107.513655

"November 24, 2009 | Lisa Nainggolan Orlando, FL - Inadequate levels of vitamin D are associated with an increase in the risk of cardiovascular disease and death, a new observational study has found. Dr Tami L Bair (Intermountain Medical Center, Murray, UT) reported the findings here at the American Heart Association 2009 Scientific Sessions. Bair and colleagues followed more than 27 000 people 50 years or older with no history of cardiovascular disease for just over a year and found that those with very low levels of vitamin D (30 ng/mL). Those deficient in vitamin D were also twice as likely to develop heart failure as those with normal levels. "We concluded that even a moderate deficiency of vitamin D was associated with developing coronary artery disease, heart failure, stroke, and death," said coauthor Dr Heidi May (Intermountain Medical Center). However, "it is not known whether this is a cause and effect relationship," she told heartwire. Because this study was observational, more research is needed "to better establish the association between vitamin D deficiency and cardiovascular disease," she noted."

Low vitamin d levels predict stroke in patients referred to coronary angiography. Pilz S, Dobnig H, Fischer JE, Wellnitz B, Seelhorst U, Boehm BO, März W. Stroke. 2008 Sep;39(9):2611-3. Epub 2008 Jul 17. PMID: 18635847 doi: 10.1161/STROKEAHA.107.513655 Conclusions- Low levels of 25(OH)D and 1,25(OH)2D are independently predictive for fatal strokes, suggesting that vitamin D supplementation is a promising approach in the prevention of strokes.

Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. Pilz S, März W, Wellnitz B, Seelhorst U, Fahrleitner-Pammer A, Dimai HP, Boehm BO, Dobnig H. J Clin Endocrinol Metab. 2008 Oct;93(10):3927-35. Epub 2008 Aug 5. PMID: 18682515 doi:10.1210/jc.2008-0784 Conclusions: Low levels of 25(OH)D and 1,25(OH)2D are associated with prevalent myocardial dysfunction, deaths due to heart failure and SCD. Interventional trials are warranted to elucidate whether vitamin D supplementation is useful for treatment and/or prevention of myocardial diseases.

25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Giovannucci E, Liu Y, Hollis BW, Rimm EB. Arch Intern Med. 2008 Jun 9;168(11):1174-80. PMID: 18541825 Conclusion Low levels of 25(OH)D are associated with higher risk of myocardial infarction in a graded manner, even after controlling for factors known to be associated with coronary artery disease.

An estimated 50% to 60% of older people have suboptimal vitamin D levels, which is a problem that could affect more than bone health. Recent cross-sectional studies have also shown an association between low vitamin D levels and cardiovascular disease, hypertension, and metabolic syndrome. In a long-term prospective study from Germany, researchers assessed whether 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were associated with all-cause and cardiovascular mortality among more than 3000 consecutive patients (mean age, 62) referred for coronary angiography.

Are statins analogues of vitamin D? Grimes DS. Lancet. 2006 Jul 1;368(9529):83-6. Review. PMID: 16815382 doi:10.1016/S0140-6736(06)68971-X There are many reasons why the dietary-heart-cholesterol hypothesis should be questioned, and why statins might be acting in some other way to reduce the risk of coronary heart disease. Here, I propose that rather than being cholesterol-lowering drugs per se, statins act as vitamin D analogues, and explain why. This proposition is based on published observations that the unexpected and unexplained clinical benefits produced by statins have also been shown to be properties of vitamin D. It seems likely that statins activate vitamin D receptors.

"Had enough about reading/hearing about Vitamin D? Well, it keeps on coming. And for my lack of surprise, the medical community in general is not catching on like wild fire. I really don't understand it. A recent study from the Heart Institute at Intermountain Medical Center in Salt Lake City (click) followed 27,686 patients greater than 50 years of age with no prior history of cardiovascular disease. The Vitamin D levels were checked and classified as such: * normal - greater than 30 ng/ml * low - 15 to 30 * very low - less than 15 The results of the study showed that patients with very low Vitamin D levels in comparison to normal had: * 77% greater risk of death * 45% increased risk of coronary artery disease * 78% increased risk of stroke * twice the risk of developing heart failure"

"A new study suggests many Americans aren't getting anywhere nearly enough of the vitamin, and it may be affecting their heart health. In the study, researchers looked at tens of thousands of healthy adults 50 and older whose vitamin D levels had been measured during routine checkups. A majority, they found, were deficient in the vitamin. About two-thirds had less vitamin D in their bloodstreams than the authors considered healthy, and many were extremely deficient. Less than two years later, the researchers found, those who had extremely low levels of the vitamin were almost twice as likely to have died or suffered a stroke than those with adequate amounts. They also had more coronary artery disease and were twice as likely to have developed heart failure. The findings, which are being presented today at an American Heart Association conference in Orlando, don't prove that lack of vitamin D causes heart disease; they only suggest a link between the two. "

"For what reason I don't know, but this January 2009 editorial by William Faloon of the Life Extension Foundation is making the rounds. Perhaps it just came available on the web. It's a good read, particularly in light of the billions and trillions of dollars the thieves & thugs in DC are about to flush down the crapper on your behalf. Some notable excerpts. A large number of new vitamin D studies have appeared in the scientific literature since I wrote my plea to the federal government. These studies don't just confirm what we knew 16 months ago-they show that optimizing vitamin D intake will save even more lives than what we projected. For instance, a study published in June 2008 showed that men with low vitamin D levels suffer 2.42 times more heart attacks. Now look what this means in actual body counts. Each year, about 157,000 Americans die from coronary artery disease-related heart attacks. Based on this most recent study, if every American optimized their vitamin D status, the number of deaths prevented from this kind of heart attack would be 92,500. To put the number of lives saved in context, tens of millions of dollars are being spent to advertise that Lipitor® reduces heart attacks by 37%. This is certainly a decent number, but not when compared with how many lives could be saved by vitamin D. According to the latest study, men with the higher vitamin D levels had a 142% reduction in heart attacks."

Strong correlations have been noted between cardiovascular diseases and low bone density / osteoporosis-connections so strong that the presence of one is considered a likely predictor of the other. This relationship has led to the hypothesis that these conditions share core pathophysiological mechanisms. Recent advances in our understanding of the complimentary roles played by vitamin D3 and vitamin K2 in vascular and bone health provide support for this hypothesis, along with insight into key metabolic dysfunctions underlying cardiovascular disease and osteoporosis. Part II, The Vitamin K Connection to Cardiovascular Health, reviews the ways in which vitamin K regulates calcium utlization, preventing vascular and soft tissue calcification while complimenting the bone-building actions of vitamin D, and also discusses vitamin K safety and dosage issues, and the necessity of providing vitamin K and vitamin A along with vitamin D to preclude adverse effects associated with hypervitaminosis D.

Zittermann A. Vitamin D and disease prevention with special reference to cardiovascular disease. Prog Biophys Mol Biol. 2006 Sep;92(1):39-48. Epub 2006 Feb 28. Review. PMID: 16600341 [PubMed - indexed for MEDLINE]