Diving deeper into your own cardiovascular risk

For most people, assessing cardiovascular risk is pretty straightforward.

Keep tabs on your blood pressure, your blood sugar, and your cholesterol.

Take account of lifestyle factors: smoking, physical activity, stress, sleep, diet, and weight.

And for many people, that’s totally sufficient.

But even though those factors constitute most of the risk of heart disease, for some people, a few other factors play an important role.

These risk enhancing factors matter for two reasons:

1. If you have aspects of your medical history that increase cardiovascular risk, it pushes us towards more aggressive treatment of your modifiable risk factors

2. Some of these risk enhancing factors are modifiable and merit direct treatment

Today, I wanted to dive into that deeper level of personalizing cardiovascular risk prediction

“Personalized cardiovascular risk assessment” by DALLE3

Think of these items as part of the way that we diver deeper into your own risk.¹

The traditional lipid panel alone may not accurately assess your cholesterol-driven risk

I’ve written before about how most doctors misunderstand the lipid panel and how there’s a lot more to this test than just measuring an LDL cholesterol level.

And while triglyceride/HDL ratio and your overall LDL-cholesterol both matter quite a bit, they don’t tell the whole story.

You should two other markers that basically everyone should have checked at least once: apolipoprotein B (aka apoB) and Lp(a).

It might surprise you to hear that LDL isn’t the best biomarker for LDL-related risk because it doesn’t measure LDL particles, it measures LDL cholesterol.²

In terms of cardiac risk, we care about total number of particles carrying cholesterol that can get into the walls of the blood vessels and cause heart disease.

It’s like measuring traffic - LDL tells you the number of people traveling up the street, but we really want to know the number of vehicles on the road - that’s where apoB comes in.

ApoB tells you the number of vehicles on the road.

You don’t necessarily need to measure apoB all the time in every person.³

But you do want to understand if apoB levels are concordant with LDL levels - because if they aren’t concordant, apoB predicts cardiac risk much better than LDL does.⁴

The people who have discordant LDL and apoB are most commonly people with insulin resistance and type 2 diabetes, precisely the people who tend to be at the highest risk of heart disease.

I’ll usually measure people’s apoB and compare to LDL to see if the numbers track - the general rule of thumb is that the apoB should be about 10% less than the LDL, and if the apoB is greater than the LDL, it says to me that apoB is the biomarker that we should track, both to understand risk and as a target of treatment.⁵

The other big lipid biomarker is Lp(a), which needs to be checked once, to help better triangulate cardiac risk.⁶

If your Lp(a) is low, you never need to think about it again. If it’s high,⁷ then it influences my likelihood of treating someone’s other risk factors which might be borderline.

Understand your kidneys with more than just creatinine

Chronic kidney disease is major risk factor for development of heart disease, but that risk is not always well captured with standard blood tests.

Anytime you get regular bloodwork done, the doctor is going to check a metabolic panel, which shows two values that inform kidney function: BUN and creatinine.

These markers are useful in many situations, but they miss two really important aspects of kidney disease, particularly as it relates to cardiac risk.

The first issue is that creatinine can misclassify patients who have chronic kidney disease as being healthy because of the way creatinine is heavily influenced by muscle mass.

If you are frail, or simply under-muscled, just looking at your creatinine can fool you with regards to your kidney function by making your kidneys look better than they are.

Whenever there is uncertainty about kidney function, cystatin C is a biomarker that isn’t influenced by muscle mass and I’ll often check this test when I’m trying to figure out a patient’s kidney function more precisely.⁸

But even more important than just being able to more accurately estimate your GFR is to know whether there is any protein in your urine.

A test called urine microalbumin provides a vitally important window in your cardiac risk as it relates to kidney issues.

And even beyond just understanding cardiac risk, the amount of microalbumin in the urine is the biggest predictor of progression of kidney disease in general.

Both of these kidney tests are simple, cheap, and widely available - cystatin C is a blood test and urine microalbumin is a urine test.

Once you see that someone has protein in their urine,⁹ it changes my management in two separate ways:

1. There are kidney-protective drugs that we can use to help slow the progression of kidney disease: ACE inhibitors/ARBs, SGLT2 inhibitors, mineralocorticoid receptor antagonists.

2. Presence of protein in the urine makes me more likely to treat other risk factors for heart disease.

The obstetric history matters when it comes to risk

PCOS, infertility, early menopause, and preeclampsia are all important things to be aware of when it comes to cardiac risk.

We don’t fully understand all of the biology here - but the relationship between the presence of these conditions and elevated risk of heart attacks and strokes is quite clear.

I ask my patients all the time about their obstetric history (and often get a lot of raised eyebrows because it seems like a weird question from a heart doctor).

And while we aren’t treating these conditions directly in my practice, when I see any of these risk enhancing conditions it influences my decision making considerably.

First, it makes me screen these patients for heart disease at a younger age than I would have otherwise.¹⁰

Second - and you might be noticing a pattern here - the presence of these factors influences my treatment decisions of the traditional stuff on the margins.

Don’t forget about inflammation

Chronic inflammation is a clear risk factor for heart disease - we know thisbecause of studies looking increased risk of heart attacks in patients with diseases like lupus and because of clinical trials like CANTOS and LoDoCo showing the benefit of treating inflammation in reducing heart disease risk.

A high sensitivity C-reactive protein is often used a biomarker here.

When the hsCRP is over 3, that’s thought to signify someone who has elevated inflammatory risk.

And while in some cases this may make a persuasive case to treat a patient with colchicine for preventing heart attacks, that’s a pretty rare thing for me to consider.

More often, the elevated hsCRP is a marker of insulin resistance and metabolic syndrome.

It’s usually a sign to double down on the lifestyle modification and think about whether medications like Zepbound or Ozempic would be helpful in reducing visceral fat and thus cardiac risk.

There’s a lot more to the personalization of cardiovascular risk

There’s a lot more that can be said about more ways to personalize cardiac risk assessment, but I think it’s better to emphasize a more meta-message.

Every patient is different and the number of permutations that exist seems almost infiniate.

There’s no single one-size-fits-all testing and treatment strategy.

Even the action items described above - which may sound straightforward - have innumerable complexities and room for personalization.

And so while it may just make sense to skip the individual assessment and put everyone on a polypill instead, I’m fully persuaded that most patients want to be treated as individuals.

So look at this newsletter as a dive into the process of personalizing heart disease risk.

If the topic seems like it connects with people, I’ll dive into it again.

1. There’s way too much to cover here in a single newsletter. So this isn’t a comprehensive look at cardiac risk, it’s an attempt to add some depth and nuance to aspects of the cardiovascular risk discussion.

2. A distinction that seems silly, but it’s actually of vital importance.

3. Although you certainly can, and in many cases it’s helpful.

4. If you don’t want to get another blood test, non-HDL performs much better than LDL, but not as good as ApoB.

5. The drugs and lifestyle changes that target LDL lower apoB, so you don’t need a whole new treatment strategy if its elevated. I gave a talk to a group of primary care doctors earlier this week and got a few questions about when to use an advanced lipid test like apoB. But I think to call it an “advanced lipid test” is a misconception. ApoB is just a better LDL. And if you’re going to use a biomarker, shouldn’t you use the best biomarker?

6. The drugs to target Lp(a) are still in clinical trials and so we don’t know yet whether targeting that is viable therapeutic strategy.

7. High will differ based on assay, but think of this as a continuous variable, not a categorical variable. Most people use a cutoff of about 50mg/dL as elevated.

8. Cystatin C is kind of similar to apoB. It’s a better biomarker than the one that we commonly use, but it isn’t used as frequently because of the fact that it wasn’t the first one that we discovered. If you were starting over in developing blood tests, you would choose cystatin C and apoB over creatinine and LDL-cholesterol.

9. Again, protein in the urine as measured by microalbumin.

10. On average, women develop heart disease about 10 years later than men do, and so I don’t always consider tests like a coronary artery calcium score or a carotid ultrasound in women in their 40s the same way that I do with men of similar ages.