Scrutinizing The Cholesterol Profile

The lipid or cholesterol profile is one of the most common batteries of blood tests. Why? Abnormal cholesterol levels may have an integral role in exacerbating a number of chronic diseases. These diseases are some of the most common, including atherosclerosis (hardening of the arteries), cardiovascular disease (heart disease and stroke) and vascular dementia. It’s even thought to be a component of age-related macular degeneration, the number one cause of vision loss in those who are at least age 60 in industrialized countries (1).

Let’s delve into the components that make up the cholesterol profile. The lipid panel is made up of several different components. These include total cholesterol, HDL or “good cholesterol,” LDL or “bad cholesterol” and triglycerides. Many people focus more on total cholesterol, HDL, and LDL and less on triglycerides. We worry about whether the levels are high enough for HDL and are low enough for total cholesterol and LDL. Is this the proper focus? With total cholesterol and LDL, this seems to be appropriate.

But with HDL it is becoming more complicated; it is less about how high the levels are and more about the functionality of HDL. There are drugs that increase HDL levels, such as niacin and the fibrates, without significantly reducing cardiovascular events. This was demonstrated in the AIM-HIGH trial (2). In this trial, niacin added to a statin drug increased HDL levels and decreased triglyceride levels without a change in the primary end point of cardiovascular outcomes. Thus, they were deemed less than satisfactory and the trial was abruptly ended. However, triglycerides get the short end of the stick. Just look lack of coverage in the mainstream media.

We will look at the different components of the lipid panel and the supposed roles they play in our health.

Let’s look at the research.

HDL — the good cholesterol that may not be so good

For years, when patients have been told their total cholesterol and LDL are high, they have asked if their HDL levels compensate for this. Of course, we in the medical community are partially to blame for fueling this thinking. More and more studies point to the importance of HDL functionality rather than the level.

In a recent study investigating a specific gene variant or mutation, those who had very high levels of HDL, a mean of 106 mg/dL, and two copies of a P376L mutation, had an increased risk of heart disease (3). In a population of 300 participants with this very high level of HDL, only one had this mutation.

When the investigators broadened the number to 1,282 participants, the results were the same. Results were consistent when they looked at a meta-analysis of 300,000 participants with high HDL. Carriers of the gene mutation, meaning they had one copy instead of two, were at a 79 percent increased risk of heart disease. Those who had this gene mutation were mostly Ashkenazi Jews of European descent. The good news is that this gene mutation is rare. However, it does show that in certain circumstances, HDL is not always good.

Lest you become too relaxed about this study, since the occurrence was uncommon, another study’s results showed that there is a U-shaped curve when it comes to HDL levels (4). In other words, those on the lowest and the highest ends of HDL levels had higher risk of death from both cardiovascular and noncardiovascular death. There were associations among HDL and other factors, like vegetable and fruit consumption, high blood pressure, diabetes, age and sex. Thus, HDL may not by itself be an indicator of heart disease death risk as suggested by the investigators in the trial. This was a large population-based study with over 600,000 participants.

In a third study, results showed that functionality is more important than HDL level (5). What is called the cholesterol-efflux capacity may be central to HDL functionality. This technique calibrates the reverse transport of cholesterol. Cholesterol is removed from a type of white blood cell in the wall of the artery, put back into the bloodstream and removed by the liver. The importance of the functionality is that a higher cholesterol-efflux capacity results in a lower risk of cardiovascular disease. In other words, you may not be able to rely on HDL levels to determine cardioprotective effects.

Triglycerides should get their due

Triglycerides need their 15 minutes of fame, just like the rest of the cholesterol profile; triglycerides may be an independent risk factor for cardiovascular disease. In a recent study, results showed that triglycerides are an independent risk factor for all-cause mortality in those with heart disease (6). But even more interesting is that those with high normal levels, those between 100 and 150 mg/dL, have a significantly increased risk of cardiovascular death. In other words, those who are still within normal limits, but at the upper end, should consider reducing their levels.

The results also showed a dose-dependent curve; the higher the levels of triglycerides, the higher the risk of death from cardiovascular disease. Measurements used included borderline high of 150-199 mg/dL, moderately high of 200-499 mg/dL and very high of >500 mg/dL. This was a secondary prevention trial, meaning the patients already had heart disease. Unfortunately, a disproportionate number of patients were men, 81 percent. However, this study had a strong duration of 22 years with data based on 15,000 patients. The weakness of this trial was its inability to control for confounders such as sickness, treatments and cause of death. Still, this signifies that triglycerides have an important role in our health.

Triglycerides are affected by diet. The elements in the diet that raise levels include sugars, grains — for some even whole grains — and starchy vegetables.

What about whole eggs? Good, bad or neutral?

Today, the debates in the medical community over eggs’ merits, detriments or neutrality continue. In a recent observational trial from Finland, results show that one egg a day did not increase the risk of heart disease (7). Whew, now we can put that debate behind us and eat eggs, right? NOT SO FAST! While the strength of the trial was its very impressive duration of 21 years, the weaknesses of the trial were huge. First, participants were asked for a four-day dietary history at the start of the trial and then never again. It was assumed that they were eating the same foods over this long time period. Second, there were no blood tests taken specifically for the study. In other words, there are no cholesterol levels for the trial. So we don’t know if one egg a day — and remember we’re making a gigantic assumption that they did eat one egg a day — had any negative impact on cholesterol levels. Third, this study population did not include women. There were 1,032 men involved. Having said all this, you could try an egg a day. However, I would highly recommend a physician’s supervision.

In my practice, I had several patients eat two eggs a day, and their total cholesterol levels went up by approximately 100 mg/dL in one month. But this is anecdotal data from my clinical experience.

In conclusion, don’t think you’re safe if you have a high HDL level. It is best to lower your triglycerides to below 100 mg/dL, and an effective way to do this is by reducing sugars, grains and starchy vegetables in your diet. However, there is subset data suggesting that the fibrate class of drugs may have benefit in those who have triglycerides of at least 500 mg/dL (6).

References:

(1) www.nlm.nih.gov. (2) N Engl J Med 2011; 365:2255-2267. (3) Science 2016; 351:1166-1171. (4) AHA 2015 Scientific Sessions; Nov. 10, 2015. (5) N Engl J Med. 2014;371(25):2383-2393. (6) Circ Cardiovasc Qual Outcomes 2016;9:100-108. (7) Am J Clin Nutr. 2016;103(3):895-901.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com or consult your personal physician.