Now that we know a little more about cholesterol and saturated fat it’s time to refocus on the villains. What factors lead to an increase in LDP particle number and oxidized LDL?

 An increase in LDL particle number has been directly associated with Metabolic syndrome (MetS). Research estimates that people with MetS are approximately 3x more likely to have an elevated LDL particle number.

 So what is MetS? The criteria have changed over the years, but here is the general consensus.

ANY three of the 5 Criteria below:

Obesity -- Waist circumference >40 inches for male and >35 inches for females

Hyperglycemia -- Fasting glucose ≥ 100 mg/dl or pharmacologic treatment

Dyslipidemia – Trigylcerides ≥ 150 mg/dl or pharmacologic treatment

Dyslipidemia (separate criteria) – HDL cholesterol < 40md/dl male, < 50 mg/dl females; or pharmacologic treatment

Hypertension -- >130 mmHg systolic or > 85 diastolic or pharmacologic treatment.

 *Note: LDL particle (LDL-P) number appears to be the most accurate marker for predicting metabolic syndrome. How do you test LDL-P. A test called NMR lipoprofile. More on this later.

 For those that meet this criteria there are some common themes. Increased LDL particles (more triglycerides to shuttle around), leptin resistance, insulin resistance and excess body fat. If you have metabolic syndrome and insulin resistance your risk of heart disease is elevated even with subclinical levels of LDL cholesterol and total cholesterol.

In addition to MetS there are several other factors that may contribute to increased particle number. These include infections, poor thyroid function, and genetic mutations (familial hypercholesterolemia or ApoE4).

Similar to elevated LDL–P an increase in oxidized LDL has four primary causes.  

1.     LDL particle vulnerability (the type of fatty acids in the membrane may account for increase in LDL oxidation). Think omega-3 vs. omega-6 ratios

2.     Antioxidant shortage (Eating processed foods without the right cofactors and enzymes)

3.     High levels of oxidative stress (smoking, stress, lack of exercise, environmental toxins and infections)

4.     Time (poor LDL clearance from the blood stream)

Here is where the rubber meets the road.

How to assess your risk of heart disease.

It doesn't hurt to take an honest look at your body composition, weight and physical fitness. Next a standard lipid panel. Never mind its inadequacies, it’s an okay starting point (see sample result.)


 What is a normal cholesterol level?

There is some debate, but in the US the cutoff for total cholesterol is 199 mg/dl. Here is where some context comes into play. Studies looking at traditional populations around the world appear to tell a different story. When you look at the Massai tribe of east Africa, Inuit, Kitiva, the Tokelau, and Pukapuka we see cholesterol levels anywhere between 140 and 250 mg/dl. The kicker is they are all relatively free or completely free of heart disease.

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Err on the side of caution

If some of your cholesterol levels are out of range further testing is recommended.

·      Total cholesterol >299 mg/dl

·      Cholesterol/HDL ratio > 4 or HDL < 40 mg/dl

·      Triglycerides >125

Since total cholesterol and LDL cholesterol are not always reliable markers it’s best to avoid taking a statin based on a single standard lipid panel. This is especially true if you intend to make lifestyle changes such as increased exercise and dietary modifications.

 Keep in mind that a single cholesterol test is of limited value. Why? Your total cholesterol can fluctuate by 35 mg/dl up or down. Triglycerides exhibit greater variability 40 up or down mg/dl. Let me be very clear that high quality large research studies indicate that LDL particle number, and not LDL cholesterol (measured on standard lipid panel), is the more significant risk factor.

One way to use the standard lipid panel and extrapolate risk would be to look at your Triglycerides (TG). If levels are below 125 mg/dl LDL particle number and LDL cholesterol coincide. However as that TG number climbs (>125) LDL particle number and LDL cholesterol diverge. The relationship stops and particle number rises. 

Life after a standard lipid panel

If your numbers are outside of the medical ranges you may want to retest with an NMR lipoprofile. This test can be ordered through most blood labs (Quest, Lab Corp, and U.S. Healthworks). As with the standard panel there’s a lot of variation with LDL particle number so it’s important to consider retesting subsequent changes in diet and lifestyle. It important to note that your doctor may order a test for apolipoprotein B (ApoB). This is an indirect way to of measuring LDL particle number. ApoB is what forms LDL or low-density-lipoproteins. 

If you’ve made it this far you’re probably wondering should I test for oxidized LDL. Based on what I’ve read Oxidized LDL is a strong risk factor for heart disease; however, measuring it directly is problematic, and it doesn’t appear to add any additional predictive value above and beyond LDL particle number. When analyzing one’s risk for heart disease some combination of looking at the big picture and using more micro-level blood markers will serve you well.

In part 3 we will talk about some other markers that may be relevant when understanding cardiovascular disease.


Please note that this information is not meant to provide medical advice or take the place of medical advice or treatment from your physician. I offer this for educational purposes.