Totally OT: following breadcrumbs to calcified aortic valve

I have posted recently about the severe stenosis of my bicuspid aortic valve. The valve is severely calcified.

According to my cardiac surgeon, both the bicuspid valve and my aortic aneurysm are genetic.

But that leaves a question: what caused the valve to be so heavily calcified that it looks like a bone on a CT scan? This wasn’t addressed by my cardiologist or surgeon who are both focused on fixing the problem.

I found the first breadcrumb this morning in The People’s Pharmacy column in my local Sunday newspaper, The Peninsula Daily News. The People’s Pharmacy has both anecdotal and research information which can be useful. When this morning’s column mentioned Lp(a) associated with aortic valve calcification my antennae perked up.

It took about 10 minutes to find these research articles.

Salient points:

  1. Lp(a), which is small particle of lipoprotein in the blood, is significantly correlated with aortic valve calcification. (Based on systematic review and meta-analysis of eight eligible studies with 52,931 participants.) Lp(a) binds to the surface then infiltrates the inner layers of the aortic valve. That triggers the cells to turn themselves into bone. That’s why my aortic valve looked like a bone on the CT scan. (This has also been seen with the mitral valve but the studies were done on the aortic valve since that’s more common.)

  2. Lp(a) level usually isn’t measured along with other lipoproteins during standard blood tests. We may know our HDL and LDL level without knowing Lp(a) level. Lp(a) is even more genetically determined than familial hypercholesterolemia and doesn’t respond to lifestyle factors such as exercise. @OrmontUS

  3. Due to the complexity of the pathogenic process, many efforts have been made to find a pharmacological target in order to prevent or arrest the aortic degeneration, unfortunately with no significant results [83]. Angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, eplerenone, nitrates, statins, denosumab and alendronic acid failed to modify the disease progression. I’m taking a statin now but it won’t change this process.

  4. I already decided to get a biological replacement valve instead of a mechanical valve. The mechanical valve requires a daily anticoagulant but, as a cancer survivor, I anticipate needing more surgery in the future. Now that I know about the calcification process I’m concerned that the biological replacement valve may get calcified. This will need more research since the bio-valves are known to “wear out” in 10-15 years anyway but no mention of Lp(a). I’m 70 and may not live that long anyway.

  5. Repatha (evolocumab) injection works to reduce low-density lipoprotein cholesterol (LDL-C) and has been shown to cut the incidence of aortic valve stenosis in half.

I don’t know yet whether I have high Lp(a) since I haven’t been tested. My CT scan showed that all my chest arteries were “unremarkable” (coronary, pulmonary, aorta, etc.). I’m going to have an angiogram in the next couple of weeks. I can’t imagine how I would be able to exercise at the intensity I do if I have significant cardiovascular disease.

Wendy

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Wendy, I don’t know anything about your case but what I continue hearing is that the problem is inflammation and the calcium is part of the healing process.

The Role of Calcium in Wound Healing

CA has been shown to reduce endothelial dysfunction and inflammation, promote EC sprouting and angiogenic factors (Binu et al., 2013; Bryland et al., 2012; Choi et al., 2015; Williams and O’Neill, 2018; Wu et al., 2019

Anti-inflammatory effects of calcium citrate in RAW 264.7 cells via suppression of NF-κB activation - ScienceDirect).

Endothelial cells form a single cell layer that lines all blood vessels and regulates exchanges between the bloodstream and the surrounding tissues. Signals from endothelial cells organize the growth and development of connective tissue cells that form the surrounding layers of the blood-vessel wall.

Blood Vessels and Endothelial Cells - Molecular Biology of the Cell - NCBI Bookshelf.

Calcium is extremely important in many aspects of cell biology. During the wound response it activates downstream molecules which are integral for membrane closure and repair. Annexins (Anxs) are calcium-dependent molecules which are rapidly recruited to sites of cell membrane injury and aid in the repair process.

The ins and outs of calcium during wound healing | Fred Hutchinson Cancer Center.

You might try to find out if you have inflammation and if so, what the causes are.

The Captain

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Another theory… The actual physics of the “OEM provided” valve are quite impressive. There are a lot of factors involved in a valve that has to operate consistently 42 million times per year or about 3.7 billion times in a 90 year lifespan. It has to close almost completely to avoid back-flow, it has to open easily, and most importantly it has to GET OUT OF THE WAY when open to avoid imparting wierd turbulence and “eddies” in the flow of the fluid it is gating. That fluid has its own unique chemical properties that create flow behaviors far more complicated than normal fluids.

Any mal-formation of the “leaves” of that valve from the “factory-optimized design” can alter its effectiveness in closing or avoiding interference with the fluid being pumped. Since the blood being pumped has unique chemical factors for clotting, any change in flow that allows some blood to “stick” in an anomoly increases the chance of clotting or inflammation. That triggers other chemical responses in the body that can snowball, producing effects which worsen the problem (since they cannot correct the root problem which is a physical anomoly in the structure of the valve).

It makes some sense to me that abnormalities in the body’s processing of calcium could lead to deposits around the moving parts in the heart which would begin growing over time leading to accelerating deterioration of their functionality.

Once the heart’s pumping efficiency is impaired, it will pump HARDER to make up for the lost efficiency, that will enlarge the heart muscle, reduce the effective size of the chambers which will make the heart even LESS efficient, which will cause it to pump HARDER and the cycle will spiral. The harder the heart pumps, the higher the pressure on the aortic arch as the blood leaves the heart and any flaw in that area will get stressed, leading to aneurysms or narrowing from inflammation.

Caveat: I am not a doctor nor am I qualified to portray one on TV.

WTH

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Well I for one am not surprised about Lp(a) being a culprit when wondering “how did this happen??!?” Heck, I’ve mentioned it often enough over the past couple of years that I wonder at anyone not making that request of their primary care provider…unless, of course, they’re one of those genetic outliers whose LDL-C is naturally at the level that mine is now (low 30s) on diet, exercise, statins and Repatha.

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If??? It’s a pretty safe bet that, at this stage of the proceedings, Wendy does have “inflammation” … simply as part of the body’s response to the ongoing injury that’s the calcified valve. Perfectly possible to measure this but would be a moot point since there is an ongoing disease process that she’s aware of.

FWIW, hs-CRP (supposedly a measurement of the degree of the inflammatory response to ASCVD) has been a routine addition to my lipid profile since the mid aughts. At a maximum of .8, it’s been one of those biomarkers that led to my primary care providers to assert that my “mildly elevated” LDL-C was of no concern…and me to believe them. Just goes to show that ASCVD can progress even when there’s no evidence of excessive inflammatory processes.

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Here’s but one review article that highlights how Lp(a) … which might suddenly look like “new” news … has actually been identified and recognised as a significant player in the pathogenesis of ASCVD for a heck of a long time…

https://www.acc.org/Latest-in-Cardiology/Articles/2022/05/01/01/42/Cover-Story-Emerging-From-the-Shadows-Lp-a#:~:text=Lp(a)%20was%20first%20identified,geneticist%20Kare%20Berg%20in%201963.&text=Berg%20recognized%20that%20Lp(a,a)%20to%20coronary%20heart%20disease.

I’ve usually cited Peter Attia’s podcast or, more specifically, his guests when mentioning this topic. Since that’s a subscription only site and most folk aren’t likely to be interested enough to pony up the modest fee to have access (until they have reason to become interested…which is almost what happened in my case) something free but a little less user friendly will have to suffice.

It’s worth noting that, given the super abundance of reproducible evidence surrounding the “culprit” status of this molecule, someone who’s found themself “suddenly” at an advanced disease state couldn’t be blamed for wondering if they’re victims of supervised neglect. I only discovered that I was a near cardiac cripple because of DIY doctoring, as I call it. Requesting specific, “advanced” testing when my PCP didn’t really think it necessary.

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This is a paper that’s been generating interest on some of the sites I follow over the past week. My husband gave me a heads-up on Friday since I’ve been bellyaching about how come no one caught my risk factors (even me) followinga return to podcast catch up now my foot is almost back to regular performance and my Z2/MAF/low lactate/ASCVD mitigation training…

https://www.nejm.org/doi/full/10.1056/NEJMoa2405182

This is particularly interesting (to me) because one thing that I feel has led to the Big Bamboozle WRT my particular lipid profile over the past 15 years or so was the use of standard risk factors in the ASCVD 10 year risk assessment calculator. My alleged risk over this period has been low enough even at age 70 to err on the side of no intervention necessary for primary prevention. Whilst maybe that doesn’t look quite so bad if one is viewing 10 years as being a decent stretch of “future” for an official Old Codger to be content with (I was 72 on Friday and it no longer looks such a decent stretch), how dumb is it to only be settling for a mere decade free of “incident” when there is one Red Flag in the standard lipid profile??? Especially when the so called “advanced” biomarker testing is there and readily available.

@captainccs human cell biology is extremely complex. Cells have many receptors, enzymes, etc. which can respond to the same substance in different ways, even in the same cell. (And more so in different cell types.)

Calcium is unusual in that it functions in signaling but is also structural (i.e. can be used to build rigid bones). Calcium ions that can signal downstream molecules for wound healing can also be assembled (along with phosphate ions) into bone.

It is essential to consume enough calcium in the diet because otherwise the body will scavenge it from the bones, causing osteoporosis.

The inflammation in the aortic valve that is caused by Lp(a) activates bone-assembly enzymes that capture calcium from the blood to ossify the valve. I’m completely gobsmacked by this – who would have thought that a heart valve could turn into a bone???

So calcium is a complex agent that can cause both healing and harm at the same time.
Wendy

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@VeeEnn you already know that you have high Lp(a). You might want to have your heart valves checked. I don’t have any symptoms so I was completely blindsided.
Wendy

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Done… and done quite a few times, in fact. My issues seem to be confined to my coronary arteries, and with zero clinical signs or symptoms whatsoever. My assumption is that, as my atherosclerotic buildup progressed, I got an equivalent increase in collateral and microcirculation. Aided and abetted by my athletic lifestyle…especially my entry into the world of formal fitness instruction in my early 50s.

First, Good luck with your upcoming surgery.
Second, Bicuspid aortic valve abnormality is associated with non-laminar flow patterns. Aortic wall remodelling secondary to altered flow patterns, about 70% of BAV patients develop aortic dilatation and depending on the “type” of flow abnormality there are different dilatation “types” of the ascending aorta.

You are very well-read on your diagnosis, and thank you for sharing. You may have already read up on this aspect of BAV. I wouldn’t be surprised.
Good Luck

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It’s also important to take K2 and D3, to enable the calcium to get from the blood to the bones: Protocol: Effects of vitamins K2 and D3 supplementation in patients with severe coronary artery calcification: a study protocol for a randomised controlled trial - PMC

I take 5,000 IU of Vitamin D on any day I don’t get sun which gives me a blood concentration of 45 ng/ml. I tried K2 from two different manufacturers but both gave me muscle pain so I stopped. I do eat kale daily.
Wendy

Kale contains K1, not K2. Here are 8 foods that contain K2: 8 Foods High in Vitamin K2 and Why You Need It

I have never had problems with the supplement, but that’s me. Been taking it about 10 years now. Recent calcium score was zero.

IP

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