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High HDL cholesterol was supposed to be straightforward good news. Then drugs designed to raise it failed to prevent heart attacks in large trials, and studies found that very high levels actually increased cardiovascular risk in some groups. The problem was never the cholesterol itself. The problem was that nobody was measuring what the HDL particles were actually doing.
The HDLfx pCAD Score (where pCAD stands for predicted coronary artery disease) reads the protein signature on your HDL particles and translates it into a single number estimating your coronary risk. It is one of the first commercially available tests to grade HDL by its functional composition rather than simply counting the cholesterol riding inside.
A standard lipid panel reports HDL cholesterol (HDL-C), the total amount of cholesterol carried inside your HDL particles. That number tells you how much cholesterol is present but says nothing about whether those particles are effective at protecting your arteries. The pCAD score takes a different approach: it measures the specific proteins riding on the surface of your HDL particles, called apolipoproteins, and combines them into one composite number.
The proteins in this score include apolipoprotein A1 (apoA1, the main structural protein of HDL) along with apolipoproteins C1, C2, C3, and C4. The balance of these surface proteins shapes how well your HDL particles pull cholesterol out of artery walls, calm inflammation, and neutralize damaging oxidized fats. A higher pCAD score suggests a protein composition pattern associated with greater coronary artery disease risk.
The foundational study behind this score examined 943 adults without a prior heart attack, all of whom underwent coronary angiography, an imaging procedure that directly visualizes blockages inside the heart's arteries. Obstructive coronary artery disease (CAD) was defined as at least 70% blockage in one or more arteries.
Each standard deviation increase in the pCAD score (standard deviation is a statistical unit measuring how far a value sits from the average) was associated with about 39% higher odds of having significant coronary blockage (an odds ratio of 1.39), even after accounting for age, sex, blood pressure, diabetes, smoking, statin use, apoA1, and ApoB (apolipoprotein B, the protein carried by LDL and other harmful particles). The score's ability to distinguish people with and without CAD, measured by a statistic called the C-index where 1.0 would be perfect discrimination and 0.5 would be no better than a coin flip, was 0.63. That is a modest but meaningful signal, roughly in line with other emerging cardiovascular biomarkers when used alone.
Among people who had confirmed coronary blockages, the score also predicted cardiovascular death over time. Each standard deviation increase was linked to about 48% higher risk of dying from cardiovascular causes (a hazard ratio of 1.48). In the overall group including people without blockages, this association was weaker and did not reach statistical significance. This suggests the score may be most informative in people who already have or are at elevated risk for coronary disease.
HDL cholesterol as a lab value has a surprising limitation: raising the number through medications has repeatedly failed to reduce heart attacks. This disconnect pushed researchers to look beyond HDL-C and toward what HDL particles actually do in the body. The most studied function is cholesterol efflux capacity, or CEC, which measures how effectively your HDL particles can pull cholesterol out of the immune cells that drive plaque buildup in arteries.
Studies measuring CEC (a related but different measurement from the pCAD score) have found that people in the highest quartile of efflux capacity had roughly 67% lower risk of cardiovascular events compared to those in the lowest quartile, independent of their HDL cholesterol levels. A meta-analysis of multiple HDL functional measures confirmed that each standard deviation improvement in efflux or antioxidant capacity was associated with 14% to 23% lower cardiovascular risk. The pCAD score approaches the same question from a complementary angle: instead of directly testing efflux, it reads the protein blueprint that determines how HDL particles behave.
Unlike established markers such as LDL cholesterol or HbA1c (a measure of average blood sugar over roughly three months), the pCAD score does not yet have universally standardized clinical cutpoints endorsed by major cardiology guidelines. The test laboratory provides its own interpretation framework, typically presenting your result as a risk tier or probability estimate. Because this is a newer measurement, treat these tiers as informative orientation rather than absolute clinical thresholds.
What matters most is where your score falls relative to your other cardiovascular risk markers and how it trends over time. A high pCAD score alongside elevated ApoB, high LDL cholesterol, or elevated hs-CRP (high-sensitivity C-reactive protein, a marker of low-grade inflammation) paints a more concerning picture than a modestly elevated pCAD score with otherwise favorable markers.
HDL particle composition shifts during acute illness, active infections, recent surgery, or flares of chronic inflammatory conditions. During these periods, HDL particles can temporarily lose protective proteins and pick up inflammatory ones, producing a score that reflects your sick state rather than your baseline cardiovascular risk. Wait at least four to six weeks after any significant acute illness or surgical procedure before testing.
Medications that change how the body processes cholesterol-carrying particles, including statins, fibrates, and niacin, alter the protein composition of HDL to varying degrees. This is not a flaw in the test. If a medication is genuinely improving your HDL particle quality, you want the score to reflect that change. However, if you recently started or stopped a lipid medication, retest after at least eight weeks on a stable dose so the result reflects your new steady state.
A single pCAD score gives you a snapshot. A trend gives you a trajectory. Because HDL particle composition responds to changes in diet, exercise, inflammation, and medication, serial testing lets you see whether what you are doing is actually shifting your HDL quality in the right direction. This is especially valuable for a score like pCAD, where individual cutpoints are still being refined and your personal trend may be more informative than any single number.
Get a baseline test when you are feeling healthy and on a stable medication regimen. If you make meaningful changes, whether starting a statin, adopting a Mediterranean-style diet, or beginning a consistent exercise program, retest in three to six months to see if the score has moved. After that, annual retesting is reasonable for ongoing monitoring. Always compare results from the same laboratory, since the assay is proprietary and values from different labs may not be directly comparable.
An elevated pCAD score should prompt a deeper look at your overall cardiovascular risk profile, not panic. Start by confirming the result with a retest in six to eight weeks to rule out a transient shift from illness or inflammation. If the score remains elevated, make sure you have a complete picture: ApoB (a count of all the harmful cholesterol-carrying particles in your blood), Lp(a) (lipoprotein(a), an inherited risk factor invisible on a standard lipid panel), and hs-CRP should all be checked if they have not been recently.
If your pCAD score is elevated alongside a high ApoB or high Lp(a), that combination points strongly toward aggressive lipid management and a conversation with a lipidologist, a physician who specializes in cholesterol and lipoprotein disorders. If your pCAD is elevated but other markers look reassuring, the score still adds useful context: it may identify residual risk that standard numbers alone would miss. In either case, a coronary artery calcium (CAC) scan can help settle the question of whether plaque has already begun to accumulate, bridging the gap between a blood marker and what is actually happening in your arteries.
HDLfx pCAD Score is best interpreted alongside these tests.