Assessment of Cardiovascular Disease (CVD) Risk, Part 2: Labs

What labs to order to assess your risk

In part 1, we discussed the major risk factors for cardiovascular disease: lipids, inflammation, and endothelial health.

In part 2, we’re going to go over how to assess these from a lab standpoint. Some of the ways to evaluate these are very well established (lipids), whereas assessment of inflammation is more nonspecific, and assessment of endothelial health is not well established at all (but we’ll try).

Lipid assessment

Scenario 1: Basic testing with standard (fasting) lipid panel.

Your basic lipid panel ordered by most physicians is going to include concentrations of total cholesterol, HDL-C, LDL-C, non-HDL-C cholesterol, and triglycerides.

Of this information, the most useful information is going to be the LDL-C, as it makes up the majority of the atherogenic lipoproteins in the blood.

It can also be useful to look at ratios of total to HDL cholesterol, as data has suggested that lower ratios are associated with lower risk of CVD.

Triglyceride levels are generally more useful to think of as a marker of metabolic dysfunction and insulin resistance, rather than a major direct contributor to atherosclerosis.

Scenario 2: Advanced lipid testing

If you’re following me, this is what you’re here for.

The test I suggest most frequently is the Cardio IQ from Quest — mostly because it has become so widely available, and gives a good amount of information for the price range (generally you can find it for ~$150). [before you go ahead and order this right now, there is another version of the Cardio IQ that also includes additional markers of inflammation that I’ll mention later — also, I have no affiliation with Quest, although if someone that works there is reading this, let’s talk.]

The Cardio IQ gives the following information that is useful in the following order:

• ApoB. As explained in part 1, we’re mainly interested in the atherogenic particles, which all contain ApoB (this includes LDL, VLDL, IDL, and Lp(a)). Above all other things, if your goal is to lower your risk of CVD, you want this number to be lower, optimally below 60 mg/dL.

• Lp(a). The measurement of Lp(a) on the Cardio IQ is especially helpful because it looks at particle numbers of Lp(a) (and is therefore measured in nmol/L). If you have yours tested and it comes back <10 nmol/L, good for you: since this level is genetically determined, you don’t need to really monitor it unless you develop problems such as severe chronic kidney disease, or use things like exogenous growth hormone that can raise levels. If yours comes back elevated (above 30-40 nmol/L or so), go review my prior post on Lipoprotein(a).

• LDL particle number (LDL-P). Because the more often you have an atherogenic particle hit the endothelial wall, the more likely it is to pass through and contribute to atherosclerosis, particle numbers of LDL are also useful to look at. In general, these levels will typically correlate with ApoB concentration — although people with metabolic dysfunction/insulin resistance can tend to have smaller LDL particles, which can result in lowish ApoB concentrations, but still elevated LDL-P. In general, I target an LDL-P under 900 nmol/L, but have seen some who suggest under 700 as well.

Inflammation assessment

The major problem with measuring inflammation is that it is nonspecific — testing doesn’t really tell you where it's coming from, so you have to use a bit of judgement of the clinical situation. Also since oftentimes these markers can change, seeing what they look like over time can be more helpful than just a single point in time.

The most easily accessible marker of inflammation is C-reactive protein (CRP). This is a liver produced by the protein in response to inflammation within the body, and is part of the immune response. CRP has a half-life of only about 19 hours, so it can quickly change. When looking at cardiovascular disease risk, we like to look at hsCRP, or high-sensitivity CRP, which can detect lower levels of CRP than standard testing. In general, we like to see hsCRP levels under 1.0 mg/L.

If you order the Cardio IQ Advanced Lipid Panel with Inflammation, you’ll get everything in the Cardio IQ panel previously mentioned, hsCRP, and you’ll also get Lp-PLA2.

From Quest’s brochure on the Cardio IQ panels: “Lp-PLA2 measures disease activity within the artery wall below the collagen or calcified cap due to activation of macrophages. The AHA and AACE guidelines list Lp-PLA2 as a strong and independent predictor of ASCVD events and may be valuable in identifying patients at increased CVD risk.”

Other tests that you can obtain include oxidized LDL (or OxLDL), which gives a sense of how much oxidative damage (due to inflammation) has occurred on your LDL proteins. This is something that can directly cause endothelial damage, contributing to atherosclerosis.

Other labs that can suggest inflammation include high levels of ferritin, high levels of fibrinogen, elevated white blood cells (generally more chronic inflammation, and low levels of albumin. Elevated levels of IL-6 and a test called myeloperoxidase (MPO) can also be measured, but again all of this is fairly nonspecific.

The CBC also can give clues to chronic inflammation, usually with a normocytic anemia (meaning slightly low hemoglobin with normal MCV) in the absence of other causes.

With all of these options, what should you do?

Personally, I just keep an eye occasionally on my hsCRP and look at clues from my other basic labs.

Why am I more of a minimalist here? Because much of managing inflammation relates to lifestyle: especially managing bodyweight and diet.

The main cause of inflammation is going to be obesity, especially when fatty liver is present. Diabetes/insulin resistance and smoking also result in inflammation.

Endothelial health assessment

This is where lab assessment gets tricky, but we have a few options to look at:

• Homocysteine. While not necessarily a marker of endothelial function per se, high levels of homocysteine can result in endothelial dysfunction (through unclear mechanisms) and increase risk of atherosclerosis. Many people who have elevated levels of homocysteine likely have MTHFR gene mutations, which result in methylation problems. Often this can be managed by taking methylated forms of B vitamins (B12, B6, folate) along with NAC.

• Asymmetric dimethylarginine (ADMA). This test is often listed as ADMA/SDMA (the other is symmetric dimethylarginine). The two of these have completely different functions, and in this case the one we care about is ADMA — which is an L-arginine derivative that is an inhibitor of nitric oxide synthase (NOS). In general, you want this level to be lower — which is achieved by diet and exercise.

• TMAO (trimethylamine-N-oxide). This is a compound that is produced when choline and carnitine are metabolized by gut bacteria, and results in endothelial dysfunction and has been shown to associated with increased risk of atherosclerosis. Studies have linked higher levels of TMAO to people who eat more red meat, and it can also be increased if you eat a lot of choline (egg yolks, liver, and salmon), or if you supplement carnitine. In my opinion, TMAO is somewhat overblown as a risk factor, but elevated levels should certainly should be taken into consideration — the main thing I would do if this is elevated is reassess my diet (although not necessarily overhaul protein sources), increase fiber intake, and add garlic supplementation.

I also like to look at labs relating to blood sugars, since these can cause endothelial damage as well — fasting glucose and HgbA1c are a common first step in assessing this, and if there is any additional concern, I would also check fasting insulin levels as well. As needed, you can go deeper, with oral glucose tolerance testing (OGTT) or just use a continuous glucose monitor.

Also, let’s not forget blood pressure and its effect on endothelial function. In general, you want your blood pressure to be run 120s/80s or less. (While risk doesn’t really show up significantly until people get into the 130s/90s, I disagree with anyone saying higher than 120s/80s on a consistent basis is optimal).

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Summary

What I’d suggest as an initial checkup:

• Lipids + Inflammation: Cardio IQ Advanced Lipid Panel with Inflammation

• Endothelium: Homocysteine, ADMA/SDMA, TMAO

Depending on findings from here, you may monitor some of these longer term. Since my homocysteine, ADMA, and TMAO are fine, I don’t monitor them on a regular basis.

What I monitor on myself — typically 2-4x/year:

• Lipids: Cardio IQ Advanced Lipid Panel

• Inflammation: hsCRP