I've had so many patients in my longevity clinic who came to me after being told everything looked fine. They've been seeing their primary care doctor for years and they've been getting their annual blood work. And every year the message was the same. Your labs look great. Just come back next year. But oftentimes when we take a closer look, we actually end up uncovering early signs of disease that have already started developing quietly in the background.
.webp "5 Critical Blood Tests EVERYONE Should Get (But Very Few Do)")
And it would be years before those routine labs would even indicate anything was wrong. So that's why in this article I want to walk you through five critical blood tests that have the potential to save your life. Now these lab tests are not routinely ordered by your primary care physician. But these tests are incredibly important because they can detect early preventable disease long before symptoms appear or before organ damage sets in.
Why Testing Is Only the Beginning
But it's not enough just to have those lab tests checked. That's actually only the beginning. As you read this article, make sure you understand the nuance of interpreting some of these test results because what you do with these results is going to be different for everyone. And also, if your PCP doesn't routinely order these tests, they may not have the experience to interpret those properly.
So, you'll need to make sure you're able to interpret those test results yourself just so that you can be your own advocate. And at the end of the article, I want to go over a lab test that is routinely ordered as part of your yearly physical, but it's often misinterpreted as normal, even though it may already be showing signs of trouble.
And as always, even though I'm a physician, I'm not your physician. So, please talk to your doctor before you make any changes to your health regimen as this article is educational only and not medical advice.
1. Lipoprotein(a), or LP Little A
Now let's start with one of the most important heart disease predictors that many people have never even heard of and that is lipoprotein A or another name for that is LP little A.
So LP little A is basically a fatty particle in your blood. And if you have high levels of LP little A, you basically triple the risk of having a heart attack in young individuals who are less than 45 years old. In fact, if you ever hear of a young person who's a picture of perfect health that out of nowhere suddenly had a heart attack, well, there's a fairly good chance they probably have an elevated level of LP little A.
And this is important to measure because LP little A is elevated in one in five Americans. So, if you pick a random person off the street, they have a 20% chance of early heart disease that we need to catch early before they get a heart attack or a stroke.
And here's something important. Elevated LP little A is almost entirely genetic. And because genes don't change, we only need to check it once in your lifetime. And you especially need to check it if you have a family history of premature heart disease. So that would be diagnosis of heart disease in a family member before the age of 55 in men and before the age of 65 in women.
Why LP Little A Is So Problematic
So the reason LP little A is so problematic is because it acts like a supercharged LDL particle. Like LDL, LP little A also carries cholesterol in the blood. But LP little A is both pro-atherogenic and pro-thrombotic. So what that means is it not only accelerates plaque formation, but it also makes those plaques more likely to rupture and cause clots. And on top of that, it can also trigger inflammation and calcium buildup of the aortic valve, which then leads to a condition called aortic stenosis, which can lead to all kinds of heart issues and heart failure.
What to Do If Your LP Little A Is Elevated
Now, if you get checked and find out that yours is elevated, we currently do not have any ways to treat high levels of LP little A specifically. Unfortunately, diet and exercise have minimal and inconsistent effects on LP little A. There are some exciting drugs on the horizon that can substantially lower your LP little A levels, but nothing's been approved yet.
So, in the meantime, if you have elevated levels, what we do is we take an extra aggressive approach to lowering your other cardiovascular risk factors. So, things like high blood pressure and insulin resistance and inflammation. And we also try to lower your LDL or apoB which is actually the next test that we need to talk about.
2. ApoB (Apolipoprotein B)
So most standard lipid panels that you get for your annual physical, they check your LDL-C which is a pretty good measure of heart disease risk but it doesn't tell the full story. So this is why I always encourage people to also check their apoB or another name for that is apolipoprotein B to get a more accurate assessment of the risk.
Why ApoB Matters More Than LDL
And here's why this matters. LDL, which stands for low density lipoprotein, is just one type of lipoprotein that carries cholesterol from the liver to the tissues. And people often refer to it as bad cholesterol because high levels of LDL can contribute to the buildup of plaque in the arteries, which then increases your risk for heart attacks and strokes.
But there's more players in the mix that also increase your risk, not just your LDL. There's also VLDL or very low density lipoprotein and IDL or intermediate density lipoprotein. These particles can also cause atherosclerosis. So that means you can have a normal LDL but still be at risk. So this is why apoB is a much better predictor of heart disease.
Each of those cholesterol carrying particles, so LDL and IDL and VLDL, they all have one apoB molecule attached to them. So when you measure apoB you're actually counting every atherogenic particle and you capture the entirety of the risk.
Now for most people apoB and LDL move together. So if your LDL is high your apoB is probably high as well. And if your LDL is low your apoB is probably low too but not in every scenario. So apoB becomes a much better predictor of risk than LDL if you have insulin resistance. So this would encompass things like pre-diabetes and type 2 diabetes and fatty liver, in some cases high blood pressure or PCOS, or if you have high triglycerides.
In the setting of insulin resistance, you often have more smaller and denser LDL particles which are actually more prone to causing plaque buildup and these particles will not be captured by the LDL-C number.
The Target ApoB Level
So with my patients who I see for longevity consultations where we often think of risk in terms of 20, 30, 40 year horizons we try to get the apoB number to below the fifth percentile of the population. So, for most people, that's below 60 milligrams per deciliter.
And this is where my recommendation may be different from your primary care physician's because in standard medicine, we're taught to use the 10-year ASCVD risk calculator. But once again, plaque is something that develops over much longer periods of time. And it starts even in early childhood. And we start seeing evidence of atherosclerosis in arteries of people in their teens and in their 20s before it eventually culminates for most people in a heart attack in their 60s or 70s. So relying on a 10-year risk assessment is too short of a window to make effective changes.
I think of it like jumping out of an airplane but not deploying your parachute until you're a few hundred feet from the ground as opposed to 3,000 ft from the ground or at whatever height you're supposed to open your parachute. If there are any skydivers out there, let me know so I can perfect my analogy.
The time to pull the rip cord on the parachute or the time that we need to intervene on heart disease should be much earlier. By the time the 10-year risk estimator that many people still use signals a problem, we've already had many years of laying down plaque that is hard to reverse at this point.
3. Homocysteine
Okay. The next test I want to talk about is homocysteine, which is just an amino acid. And high levels of homocysteine are considered to be an independent risk factor for heart attacks and strokes and even dementia. And homocysteine is also a good marker of your B vitamin status, especially B12 and B9 which is folate, and vitamin B6.
So the problem here isn't that you have homocysteine. It's normal to have homocysteine because it's just a natural byproduct of protein metabolism. Where we run into a problem is when there's too much homocysteine in your blood.
The Factory Smoke Analogy
So think of homocysteine like factory smoke. A little smoke is normal and it's expected when the factory is running properly. But if the exhaust system isn't working right, the smoke then just starts building up and polluting everything around the factory. So what keeps your body's exhaust system in this analogy running smoothly? Well, that would be B vitamins, especially vitamins B12 and B9, which is folate, and vitamin B6, which is pyridoxine.
These B vitamins are part of a very tightly regulated metabolic process. Folate and B12 are required for the remethylation of homocysteine to methionine. And B6 is necessary for the transsulfuration pathway that converts homocysteine to cystathionine. In other words, these B vitamins act like filters or converters that help recycle homocysteine back into harmless or even more useful compounds. But if we have a deficiency in any of these B vitamins, well then homocysteine starts accumulating and rising to unhealthy levels.
The MTHFR Gene
And one important side note here, some people actually have a variation in their MTHFR gene which affects their ability to process or metabolize homocysteine. So that's another test that I frequently order alongside homocysteine which helps us guide proper therapy and assess cardiovascular risk.
And if there is a mutation in the MTHFR gene, that's when I may recommend my patients to use methylated versions of B vitamins to lower those homocysteine levels. But that's a whole other topic for another day because there's a lot more nuance that goes into that.
The Target Homocysteine Level
Oh, and another important side note with homocysteine. Your normal levels may depend on how the lab reports it. And the normal ranges may vary by age and sex. But for most of my patients, I actually recommend they try to get their homocysteine levels to below 10 and maybe even lower if there's increased risk factors for heart disease or strokes or dementia.
4. Uric Acid
Okay, the next test that we need to talk about is uric acid. Now, if you're like most Americans, you've probably never had this checked because it only gets brought up when we're dealing with gout. But high uric acid is not just about gout. It's also a very good early marker of insulin resistance and high blood pressure and heart disease.
There's multiple cohort and mechanistic studies that demonstrate that higher uric acid levels are positively correlated with insulin resistance in both diabetic and non-diabetic populations. And we have studies that estimate that insulin resistance accounts for roughly 30 to 40% of the link between elevated uric acid and high blood pressure.
So, this is a test I recommend checking at least yearly if you're perfectly healthy because that will help you spot the problems before you notice any changes in other lab tests like hemoglobin A1C or fasting insulin. And I recommend checking it more frequently if there's already issues with insulin resistance or high blood pressure or heart disease or fatty liver.
The Target Uric Acid Level
Now, one important caveat here. If you read your lab report, depending on the lab, most of them will say it's normal if your uric acid is under seven. But most labs look at it through the lens of gout. And you want to look at it in terms of metabolic and cardiovascular health. So in my patients, I try to get people down to below 5.5. This is the level where we see marked improvements, reversals of high blood pressure and insulin resistance.
But we do have to be cautious when interpreting uric acid levels as sometimes exercise can cause transient elevations in uric acid, at which point we get several measurements and we start looking at trends as opposed to individual snapshot readings.
5. Cystatin C
Okay. The next blood test that I recommend is called cystatin C, which is a more accurate measure of your kidney function than what you normally get from your routine basic metabolic panel where we use creatinine to assess the kidneys. I've seen so many patients whose labs look normal on paper when the kidney function was calculated based on creatinine. But then we checked cystatin C and we uncovered that there's already damage happening in the kidneys.
The Problem With Creatinine
So the problem we run into with creatinine is it comes from muscle breakdown and the number really depends on muscle mass. So if you're older or lean or if you have low muscle mass, your creatinine may look perfectly normal even if your kidneys are not doing that well. On the other hand, if you have above average muscle mass or if you're dehydrated, well then creatinine can appear higher or look abnormal even though your kidneys are doing fine.
Why Cystatin C Adds Clarity
So this is where checking cystatin C can add quite a bit of clarity. It's not affected by muscle mass or diet. And every cell in your body makes cystatin C and your kidneys clear it at a steady rate. So this makes it a much purer reflection of kidney filtration.
But important side note with cystatin C though, it's not entirely free from non-kidney related influences. It can also be affected by factors like obesity and inflammation or thyroid dysfunction. So that's why in an ideal world we actually use both creatinine and cystatin C to get the accurate assessment of your kidneys because cystatin C levels start showing problems with filtration a lot sooner before we spot those issues with creatinine.
Bonus: ALT, the Routine Test That Is Often Misread as Normal
Now, let's talk about a lab test that is routinely ordered as part of everyone's annual blood test, but it's often mistakenly interpreted as normal, even though it may already be showing signs of disease. And I'm talking about your liver function test, and more specifically, your ALT, which stands for alanine aminotransferase.
So, if you get this test, the lab report will say it's normal with values all the way up to 40 units per liter. But the problem with this definition is what's considered normal has drifted upwards over time because the average population has become less healthy. In fact, in the 1970s, the upper limit of normal for ALT was probably closer to 25 than 40.
And this is happening because of how laboratories determine normal limits. So labs take the mean of the quote unquote healthy population and they say, "Okay, two standard deviations around the mean is what we consider within normal limits." But the ALT mean has been trending up probably due to the increasing prevalence of fatty liver disease. I think the latest estimates show that almost a third of the world population has fatty liver disease at this point and most of those cases are undiagnosed.
The Target ALT Level
So if you look at the American College of Gastroenterology guidelines, they consider a true healthy ALT level to range from 29 to 33 in males and 19 to 25 for females. But even that is a little too high. So with my own patients, I recommend trying to get that ALT level down to below 25.
Anything above that probably warrants a further investigation and workup, especially for fatty liver disease and insulin resistance because fatty liver once it progresses is now one of the leading causes of liver transplants in the US and Europe. And it can be devastating if we let it progress unchecked without intervention.
All right, so this is not an exhaustive list of all the labs I recommend. With my own patients, we usually get quite a few more lab tests depending on their individual circumstances or their goals. So, if there is a lab test that you want me to cover in my future articles, let me know in the comments below.
Hope this was helpful. Stay healthy and I'll see you in the next
Frequently Asked Questions (FAQ)
Why do I need blood tests that my primary care doctor does not order?
These five tests are not routinely ordered by primary care physicians, but they can detect early preventable disease long before symptoms appear or before organ damage sets in. Often, patients told their labs look great actually have early signs of disease developing quietly in the background.
What is LP little A and who should get it checked?
LP little A, or lipoprotein A, is a fatty particle in your blood that acts like a supercharged LDL particle. It is elevated in one in five Americans, and high levels can triple the risk of a heart attack in young individuals under 45. Since it is almost entirely genetic, you only need to check it once in your lifetime, especially if you have a family history of premature heart disease.
Can I lower my LP little A with diet and exercise?
Unfortunately, diet and exercise have minimal and inconsistent effects on LP little A. There are some exciting drugs on the horizon, but nothing has been approved yet. In the meantime, the approach is to lower your other cardiovascular risk factors more aggressively, such as high blood pressure, insulin resistance, inflammation and LDL or apoB.
Why is apoB a better test than LDL?
LDL is just one type of cholesterol carrying particle. LDL, IDL and VLDL all have one apoB molecule attached, so measuring apoB counts every atherogenic particle and captures the entirety of the risk. It is especially useful if you have insulin resistance, pre-diabetes, type 2 diabetes, fatty liver, high blood pressure, PCOS or high triglycerides.
What apoB level should I aim for?
For most people, the target is below 60 milligrams per deciliter, which is below the fifth percentile of the population. Relying on the standard 10-year ASCVD risk calculator is too short of a window because plaque develops over decades.
What does homocysteine tell me?
High levels of homocysteine are an independent risk factor for heart attacks, strokes and even dementia. It is also a good marker of your B vitamin status, especially B12, B9 (folate) and B6. For most patients, the recommendation is to get homocysteine levels below 10, and maybe even lower if there are increased risk factors.
Why should I check my uric acid if I do not have gout?
High uric acid is also a very good early marker of insulin resistance, high blood pressure and heart disease. Most labs call it normal if it is under seven, but for metabolic and cardiovascular health the recommended target is below 5.5.
Why is cystatin C better than creatinine for checking kidney function?
Creatinine comes from muscle breakdown, so it depends on muscle mass and can look normal in older, lean or low muscle mass people, even when the kidneys are not doing well. Cystatin C is not affected by muscle mass or diet and starts showing problems with filtration sooner. Ideally, both are used together.
Why is a normal ALT result sometimes misleading?
Labs say ALT is normal up to 40 units per liter, but normal has drifted upwards over time as the population has become less healthy. In the 1970s, the upper limit of normal was probably closer to 25. The recommended target is below 25, and anything above that warrants further investigation for fatty liver disease and insulin resistance.
Conclusion
Being told that your labs look fine does not always mean everything is fine. LP little A, apoB, homocysteine, uric acid and cystatin C can reveal early signs of heart disease, insulin resistance and kidney problems years before routine labs show anything wrong. Even a routine test like ALT may be misinterpreted as normal when it is already showing signs of trouble.
Just as important as getting these tests is understanding how to interpret them, so that you can be your own advocate. Talk to your doctor before making any changes to your health regimen, because what you do with these results is going to be different for everyone.