Apolipoprotein B is the protein that wraps around every atherogenic lipoprotein particle, including LDL, VLDL, IDL, and Lp(a). Each of these particles carries exactly one ApoB molecule. That means measuring ApoB gives you a direct count of the total number of particles capable of depositing cholesterol in your artery walls.

A 2019 analysis published in JAMA Cardiology examined data from nearly 400,000 participants and found that ApoB was a stronger predictor of cardiovascular events than LDL-C, particularly in patients with discordant values (where particle count and cholesterol levels didn't match). The European Atherosclerosis Society now recommends ApoB as the preferred marker for assessing cardiovascular risk.

ApoB is particularly valuable in patients with metabolic syndrome, insulin resistance, or diabetes, conditions where LDL-C often underestimates true risk because particles tend to be smaller and more numerous.

Some labs offer LDL particle number (LDL-P) testing via NMR spectroscopy, which also counts particles. While this provides similar information, we've found ApoB more clinically useful: it's simpler, more widely available, less expensive, and captures all atherogenic particles (not just LDL). The European guidelines now recommend ApoB as the preferred metric, and that's what we use at Griffin Concierge Medical.

Lipoprotein(a) is one of the most underappreciated risk factors in cardiovascular medicine. It's an LDL-like particle with an additional protein, apolipoprotein(a), attached. This extra protein makes Lp(a) both more inflammatory and more likely to promote clot formation than regular LDL.

Here's what makes Lp(a) unique: your level is 80-90% genetically determined. Unlike LDL cholesterol, Lp(a) doesn't respond meaningfully to diet, exercise, or most cholesterol-lowering medications. Statins don't lower it. Neither does lifestyle modification. Your Lp(a) at age 25 will be roughly the same as your Lp(a) at age 65.

Approximately 20% of the population has elevated Lp(a), defined as above 50 mg/dL or 125 nmol/L. These individuals have a significantly increased risk of heart attack, stroke, and aortic valve disease, independent of their other risk factors. Many have no idea they carry this genetic burden because their doctors have never ordered the test.

If your Lp(a) is elevated, you can't change it directly, but you can compensate by being more aggressive with the risk factors you can control. This might mean targeting a lower ApoB, being more vigilant about blood pressure, or considering earlier imaging to assess whether disease has already developed.

Important: Because Lp(a) is genetically fixed, you only need to test it once in your lifetime. If your doctor has never ordered it, ask.

Atherosclerosis isn't just about cholesterol accumulation; it's fundamentally an inflammatory disease. The plaques that rupture and cause heart attacks are typically inflamed plaques, characterized by immune cell infiltration and structural instability. You can have significant plaque burden with low inflammation (relatively stable), or modest plaque with high inflammation (dangerous).

High-sensitivity CRP is a marker of systemic inflammation produced by the liver. While it's not specific to the cardiovascular system (it rises with any inflammatory process), elevated hsCRP in the absence of obvious infection or inflammatory disease suggests ongoing vascular inflammation.

The JUPITER trial demonstrated that patients with low LDL-C but elevated hsCRP still benefited significantly from statin therapy, suggesting that inflammation itself is a treatment target, independent of cholesterol levels. More recently, the CANTOS trial showed that directly targeting inflammation (with a drug called canakinumab) reduced cardiovascular events even without lowering LDL.

We use hsCRP as part of our risk stratification and to guide the aggressiveness of treatment. A patient with borderline lipids but persistently elevated hsCRP may warrant more intensive intervention than their cholesterol alone would suggest.

While we've focused on advanced markers that go beyond the standard lipid panel, there's one pattern within that standard panel that deserves special attention: the combination of low HDL cholesterol and elevated triglycerides.

This pattern is one of the most powerful predictors we have. When we see HDL levels in the 20s or 30s combined with triglycerides above 150 mg/dL, especially in younger patients, it's not a question of if cardiovascular problems will develop, but when. This combination signals underlying metabolic dysfunction: insulin resistance, impaired fat metabolism, and an inflammatory state that accelerates atherosclerosis.

The standard lipid panel remains a valuable screening tool precisely because it can reveal this pattern early, often years or decades before clinical disease manifests. It's frequently our first indication that something needs attention, prompting deeper investigation with the advanced markers described above.

Homocysteine is an amino acid produced during the metabolism of methionine (found in protein-rich foods). Under normal circumstances, homocysteine is rapidly converted to other compounds through pathways that require B vitamins, particularly folate, B6, and B12.

When these pathways are impaired, due to genetic variants like MTHFR mutations, B vitamin deficiencies, or certain medications, homocysteine accumulates. Elevated levels are associated with endothelial dysfunction (damage to the artery lining), increased clotting tendency, and accelerated atherosclerosis.

Unlike many cardiovascular risk factors, elevated homocysteine is often correctable. In many cases, targeted B vitamin supplementation (methylfolate, methylcobalamin, P5P) can normalize levels. However, the clinical trials on homocysteine-lowering haven't shown the dramatic reduction in events that was initially hoped for, suggesting that homocysteine may be more of a marker than a direct causative factor, or that the damage occurs before levels are detected and corrected.

We still include homocysteine in our panel because it provides information about methylation status and B vitamin adequacy, and very high levels (>15 µmol/L) do appear to independently increase risk.