Cholesterol (Part III) - The Case For Action
The first two parts of this series on cholesterol discussed the need to clarify some notions about this topic that can help us better understand the impact of this molecule on the body, as well as to know the best dietary interventions to optimize our health in this area. With this final part, the aim is to integrate this information so that I can explain my perspective on the most appropriate way to approach this issue, in light of my interpretation of current knowledge.
1 - Assessment
When we begin assessing someone's lipid profile, we should obtain the most accurate values possible for the most important metrics. The initial thought should always consider the number one concern: how can I assess the risk of my patient developing atherosclerotic disease? This will be the main factor for our primary outcome: reducing the probability of cardiovascular disease.
Since the theme of this series of articles is cholesterol, the best way to assess the mentioned risk will be to direct our evaluation to LDL, as these are the lipoproteins with the greatest atherogenic potential. Although the most commonly used form of assessment is LDL cholesterol concentration (c-LDL), we have seen that this method will never be as adequate as counting the number of LDL particles (p-LDL); or, even better, counting the number of apolipoproteins-B (ApoB), since it is present in all atherogenic lipoproteins (which, although mostly LDL, can also be of other types), in a 1:1 ratio, so it appears as the most approximate form of evaluation.
In addition to this, it becomes essential to measure Lipoprotein (a) - Lp(a), due to its atherogenic potential, even if only in an initial assessment, as it is related to genetic polymorphisms.
Atherogenic potential assessment
ApoB -mg/dL
p-LDL - nmol/L (alternatively)
Lp(a) - nmol/L
HDL, due to its involvement in reverse cholesterol transport, by eliminating excess cholesterol through the liver, should also be a point to assess. Their particle number will be the best measure; however, since these lipoproteins are related to Apolipoproteins A (ApoA), in this case, counting the number of these apolipoproteins will not bring an advantage because each HDL has more than one ApoA.
HDL assessment
p-HDL - µmol/L
Due to their importance and the possibility of targeted therapeutic intervention, particularly dietary, triglycerides should also be evaluated.
Triglyceride assessment
Triglycerides - mg/dL
Although these are the parameters whose evaluation may be most useful for our intervention, the rest of the lipid panel may provide some additional information, such as the measurement of LDL particle sizes (the larger ones belong to pattern A and the smaller and denser ones to pattern B); and even the most common evaluations of c-LDL, c-HDL, and total cholesterol, may help if we do not have the other assessments available.
2 - Intervention
Lifestyle
When we seek to intervene in the context of lipid metabolism to reduce our cardiovascular risk, lifestyle intervention, primarily in diet, will be very important. As we saw in Part II of this series, it will be essential to advise patients to reduce consumption of saturated and trans fat.
The first is easily identified because it remains solid at room temperature and can be found in red meat and cheese, for example.
The second is a type of unsaturated fat that exists naturally (in residual amounts) in various foods (meat and dairy, for example); but is mainly represented in foods produced after industrial modification of oils and fats (e.g., margarine, biscuits and chips).
Consumption of these types of foods should be more moderate due to the higher amount of triglycerides they contain and, consequently, the possibility that they, when absorbed, promote an increase in circulating LDL particles; or even avoided, in the specific case of trans fats, due to the increased inflammatory potential that industrially modified foods represent.
Considering that, as we also saw, excessive carbohydrate consumption also promotes an increase in circulating triglycerides, an intervention to decrease the consumption of carbohydrate-rich foods should also be carried out. As mentioned regarding trans fats, carbohydrates also have a higher inflammatory potential (in their case, due to increased insulin resistance when consumed in excess), so consumption should also be reduced for this purpose, since promoting inflammation is an essential mechanism for the development of atherosclerosis and subsequent cardiovascular problems.
Likewise, the intake of foods that promote intestinal microbiota health will also play an important role here (e.g., kefir, kombucha), as maintaining a healthy gut flora will allow keeping lipid metabolism regulation mechanisms in enterocytes finely tuned and, once again, prevent inflammation promotion.
Dietary care
Moderate consumption of saturated fats
Avoidance as much as possible, of trans fats intake
Maintenance of an adequate carbohydrate intake
Ingestion of foods that promote intestinal microbiota health
*opt for organic foods in all cases.
However, the potentially inflammation-regulating mechanisms of these foods cannot be individually addressed within the scope of this series, as they require extensive individual review on their own.
It is also in this area that promoting a healthy lifestyle (outside the realm of nutrition/diet) can have a significant impact on lipid metabolism. Unfortunately, measures such as appropriate physical exercise, notably aerobic exercise, or sleep regulation, have shown little significant direct effect on reducing individual cholesterol levels. However, education in this area should always take place because they will always have positive effects on reducing weight (and this on the inflammatory impact of obesity) and blood pressure, for example, which are two major risk factors for the development of atherosclerosis. Furthermore, smoking, besides being a promoter of high blood pressure, is also, individually, a risk factor for the deposition of atherosclerotic plaques, so it should also be addressed (in parallel with excessive alcohol consumption, which has a similar effect on blood pressure, promotes high carbohydrate levels, and has all the other harmful effects known to all of us).
Habits
Promotion of physical exercise (especially aerobic)
Maintenance of proper sleep habits
Smoking cessation
Alcohol consumption avoidance
Despite all that has been said so far, sometimes pharmacological intervention is necessary as a complement to all the actions already listed. The current options are several:
Pharmacological therapy
Statins
First-line drugs
Inhibit an enzyme (HMG CoA Reductase), reducing cholesterol production in the liver (link)
The most potent are atorvastatin and rosuvastatin
Ezetimibe
Commonly used as a second-line drug (an adjuvant to statins)
Blocks the Niemann-Pick C1-like receptor in intestinal cells where cholesterol absorption occurs (link)
Bempedoic acid
A new therapy that can be used in conjunction with the two previous options
Antagonizes ATP citrate lyase, which, consequently, being involved in hepatic cholesterol synthesis (through the mechanism of HMG CoA Reductase), will decrease that production (link)
Fibrates
Older drugs mainly used to reduce triglyceride levels (but also LDL, in smaller amounts)
Reduce the availability of substrates for triglyceride production in the liver (link)
Promote LDL clearance, increase reverse cholesterol transport and decrease the oxidative potential of smaller and denser LDL, through lipoprotein lipase (link)
PCSK9 inhibitors
Prevent the degradation of LDL receptors on the surface of cells, thus promoting the removal of these particles from the bloodstream (link)
Very expensive and, in many countries, their individual prescription is not possible except through hospital pharmacies
The world of cholesterol and lipid metabolism, as we have seen in this series of three articles, is constantly a matter of discussion, as new scientific data is obtained. With this work, I intend to clarify some of the concepts related to this topic (mainly those that usually create more confusion) and discuss the various paths for addressing lipid metabolism disorders, always aiming to promote the cardiovascular health of each individual.
Nothing found here is the final word on each topic, but rather a particular view, based on the scientific data I know and consider is the most robust in this area.
I hope, in this way, to contribute to a continuous and healthy discussion on a topic that, given the increasingly significant impact it has on the world population, especially in the most developed countries, affects, more or less directly, all of us.
