Lipoprotein(a) series. Part 1. What’s the risk?

Lipoprotein(a) is a lipoprotein particle. Like the LDL particle, it increases the risk of cardiovascular disease. Before diving into details about just what Lipoprotein(a) is, let’s get a handle on just how much of an impact high Lipoprotein(a) levels can have.Lp(a) blood level show a dose-response relationship to cardiovascular disease risk in multiple studies, and Lp(a) is now widely considered a reliable marker for CVD risk.

Here is a graph showing ~4-fold increased risk at >95th-percentile Lp(a) level:

[Above is adjusted for age (left) and multifactorially (right). The multifactorial adjustment is for age, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apoB, BMI, hypertension, DM, smoking, lipid-lowering therapy, and, for women, menopause and HRT.]

Here are the same data represented with a Kaplan-Meier curve.

As we can see, the unadjusted, >95th percentile Lp(a) associates with >2x lifetime incidence of myocardial infarct (heart attack).

At 80-years-old, 15% at the 22nd percentile or below but 30% at 95th percentile or above will have had a myocardial infarction.

30% of people at below the 22nd percentile but 40% at above the 95th will have cardiovascular disease (CVD).

In other words, Lp(a) = more frequent, more severe cardiovascular disease.

Why did investigators adjust for those variables in the first graph? Because risk factors go together: smoking goes with bad diet, lack of exercise, low income, etc. So if you do a study and conclude smoking causes X, it could actually be all those other things causing X.

So what investigators do is use statistical methods to estimate what the data would look like with all variables of non-interest equal, and just the variable of interest changing.

This multifactorial adjustment usually causes the risk attributed to the variable of interest to decrease relative to the unadjusted risk. Yet in this study, the risk doubled after adjustment. This is unusual, and investigators noted this but couldn’t explain it.

Could it be that somehow Lp(a) protected participants from diabetes, stopped them from smoking, reduced cholesterol, caused lower blood pressure? We may look at this more later in the thread.

Here is one more study (2016) showing the same epidemiological trend, using two different assays for Lp(a), analyzing data from the UK, showing the same results.

Again, we see a 2- to 4-fold increase in risk in CVD. Most people have ~1/3 chance of dying from CVD. CVD probably increases Alzheimer’s risk as well. This means that at the upper quintile for Lp(a) blood levels, we expect a large increase in absolute risk of both CVD and other diseases. It’s a really big deal.

That concludes our introduction to the importance of Lipoprotein(a). We will revisit all of this and more as we unpack our discussion about this marvelous and terrible lipoprotein.

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