Preventing Calcified Arteries

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Coronary artery disease (CAD) remains the #1 killer of Americans. A late stage component of advanced atherosclerosis is the build-up of bone-like calcified tissue in the media and intima of the artery wall. This vascular calcification is complex and still poorly understood but appears related to traditional cardiovascular disease (CVD) risk factors and inflammation. Recent evidence suggests that it is an active cell-mediated process following the transformation of vascular smooth muscle cells into these osteoblast-type (or bone like) cells. Increasing the calcium content of coronary arteries has been shown to be of value in the risk stratification of asymptomatic patients with possible CAD in emergency rooms. The amount of calcium in the coronary arteries is measured by electron beam computed tomography (CT). Increasing bone-like tissue in the major coronary arteries has now become a well-established additional risk factor for a heightened risk of having a heart attack and other CVD event over the next 10 years. The coronary artery calcium (CAC) score (a.k.a. Agatston score) is increasingly being used to help physicians better predict their patients’ artery health and their future risk of a having a heart attack. The CAC score adds additional predictive value on top of other established CVD risk factors such as dyslipidemia, elevated blood pressure (BP), increasing age, smoking, gender, inactivity, inflammation (e.g. hsCRP), family history, and insulin resistance/type 2 diabetes. It is likely that further build-up of coronary calcium deposits or an increasing CAC score would be indicative of CAD progression and an increasing risk of a future CVD event.

Can Diet Promote or Slow Artery Calcification?

Research has shown that calcium build-up in arteries is the result of normal vascular smooth muscle cells (VSMC) changing into bone-like cells. This pathologic process appears to result in part from an increase in intracellular sodium and calcium. More salt inside the VSMCs of mice has been shown to promote this pathological conversion into these bone-like cells that accumulate calcium. Increased dietary salt intake is a major reason that 90%+ of all American end up with hypertension (HTN). High-salt diets have long been known to contribute to thicker and stiffer aortas and other major arteries. High-salt diets and HTN damage the endothelial cells and speed up the atherosclerotic process and inflammation. It also seems likely that a high-salt diet may also directly promote the conversion of normal VSMCs into osteoblast-like VSMCs by increasing the sodium and calcium content of these VSMCs. Reducing dietary salt helps reverse aortic stiffness as measured by pulse wave velocity (PWV) and this reduction in arterial stiffness appears to be at least partially independent of changes in BP. Over time, a healthier low-salt, higher-potassium DASH-style diet may alter electrolyte levels in VSMCs by lowering intracellular sodium and calcium levels. This electrolyte change likely slows the secretion of scar-like connective tissue into the artery wall and slows the buildup of calcium in artery walls, thus reducing the tendency for arteries to become thickened, more calcified, and stiffer, leading over 90% of Americans to end up with HTN by their late 70s or early 80s.

A recent study examined the effects of a diet high in potassium-rich foods to see if they may be protective against pathogenic vascular wall calcification. Dr. Yabing Chen and colleagues at the University of Alabama (UAB) examined the impact of varying the dietary potassium content on the buildup of calcium in their arteries. Dr. Chen showed that mice fed higher potassium diets ended up with reduced calcium buildup in their arteries. The UAB researchers also grew cross sections of mouse arteries in a medium with varying levels of calcium and grew mouse VSMCs in culture to examine the mechanism by which increased potassium may help prevent the conversion of these VSMCs into bone-like cells. The mice used in the feeding study were genetically prone to develop atherosclerosis. They were fed diets with a 0.3, 0.7, and 2.1% potassium content. They found a significant increase in vascular wall calcification on the lowest potassium diet compared to the moderate potassium diet. The mice fed the highest potassium diet experienced a marked inhibition of vascular wall calcification. They also determined that the mice fed low potassium diets had stiffer aortas, while those fed the highest potassium diet had far less artery stiffening. The dietary potassium intake correlated with the potassium content of the mice’s serum. The researchers next examined the smooth muscle cells in culture. This part of their study showed lower potassium content led to elevated calcium levels inside these smooth muscle cells that caused them to change into bone-like cells. The results of this excellent study show for the first time that a lower dietary potassium intake leads to lower serum potassium levels which contribute to the stiffening and increased calcification of arteries. While this research was done in mice, it is more than likely that this same mechanism plays a role in the stiffening and increased calcification of human arteries as well.

Lack of Vitamin K2 May Contribute to Artery Calcification

The evidence is growing that a lack of vitamin K, and especially vitamin K2, appears to be a contributing factor in deposition of excess calcium into the artery walls rather than into the bones. Vitamin K2 involvement in artery calcification appears to be via the inhibition of vascular foci needed for the carboxylation of Gla proteins. These proteins that help regulate calcium uptake by cells and too little vitamin K2 results in reduced bone matrix production and weaker bones and contributes to the deposition of calcium in bone-like cells forming inside artery walls filled with atherosclerotic plaques. It is known that the gut bacteria of the genus bacteroides are responsible for the conversion of vitamin K1 into vitamin K2 in the gut. A diet low in foods rich in vitamin K1 and/or the alteration of gut’s microbiome that reduces bacteroides species needed to help convert Vitamin K1 to K2 may contribute to insufficient vitamin K2 levels in the body. This change in gut microbes thus contributes to both weaker bones and increased calcified artery walls.

Another reason to suspect that inadequate vitamin K activity is involved in increased CAC scores is the growing evidence that the use of Coumadin (a.k.a. warfarin) increases the calcification of soft tissue, including the artery wall. Warfarin is a vitamin K antagonist reducing both blood clotting and proper transport of calcium into bones rather than into soft tissues. Endogenous inhibitors of normal calcium uptake in bones appear to also prevent arterial calcification. One key inhibitor is matrix Gla protein, a vitamin K–dependent protein synthesized by VSMCs. Warfarin, a drug prescribed because it reduces blood clotting by blocking vitamin K dependent proteins helps prevent blood clots from forming in the heart and traveling to the brain where they can cause a stroke. Unfortunately, warfarin appears to also block the formation of the Gla proteins needed to strengthen bones while increasing the uptake of excessive calcium by soft tissues including those VSMCs, thus transforming them into bone-like cells inside the artery wall. While warfarin does help reduce strokes in the short term, over the longer term this vitamin K blocking drug appears to contribute to both an increased risk of osteoporotic fractures and an increased calcification of soft tissues including the artery wall.

Fiber and Acetate Increase Bacteriodes

In a mouse study, Dr. Kaye and associates showed that increasing dietary fiber and/or acetate helped prevent elevated blood pressure and thickening and hardening of the heart muscle and blood vessels. The beneficial bacteria were Bacteriodes and Bifidobacterium, the latter help ferment the fiber to acetate. The Bacteroides are from the same bacteria genus known to help convert vitamin K1 to K2 in people. Higher intake of fiber or simply giving the mice acetate in their drinking water both appeared to work in part by down regulating heart and kidney Egr1, a master cardiovascular regulator. Higher levels of Egr1 promote inflammation and fibrosis and dysfunction in the heart and kidneys. The researchers conclude: “A diet high in fiber led to changes in the gut microbiota [increased Bacteroides & Bifidobacterium and reduced Prevelotella] that played a protective role in the development of CVD.”

Vitamin D: Too Much or Too Little May Promote CAC

The role of vitamin D and its derivatives in preventing or promoting the calcification of soft tissues and major arteries is complex. There is evidence to implicate both a deficiency of vitamin D but also high doses of supplemental vitamin D with an increased risk of increased CAC scores. It seems likely that serum 25-OH-D levels in the 20 to 40ng/ml range would be both sufficient to prevent deficiency but also not high enough induce vitamin D toxicity – either of which might contribute to artery calcification.

Bottom Line: Evidence continues to mount that a low-salt DASH-style diet can effectively lower elevated BP and alter numerous other known and suspected CVD risk factors. Some of these risk factors are also being linked to an elevated risk of fibrotic changes to the arteries, heart, and kidneys that are increasingly being associated with the accumulation of calcium in the artery wall and with an elevated risk of advanced CAD, renal failure, and heart failure.

By James J. Kenney, PhD, FACN

References: 

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