|Year : 2019 | Volume
| Issue : 1 | Page : 1-4
Dyslipidemia and cardiovascular diseases: Science or fairy tale
Basil Nwaneri Okeahialam
Department of Medicine, University of Jos and Jos University Teaching Hospital, Jos, Plateau State, Nigeria
|Date of Submission||09-Jun-2019|
|Date of Acceptance||16-Jun-2019|
|Date of Web Publication||22-Oct-2019|
Prof. Basil Nwaneri Okeahialam
Department of Medicine, Jos University Teaching Hospital, Jos, Plateau State
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Okeahialam BN. Dyslipidemia and cardiovascular diseases: Science or fairy tale. Nig J Cardiol 2019;16:1-4
The year 2018 marks the 4th year since the Nigeria Cardiac Society introduced an annual lecture in honor of late Prof. Asuquo Antia, the first President of the Society. I consider myself privileged to be considered worthy to give this year's lecture. I thank Professors Sani and Karaye for nominating me and the executive of the Nigeria Cardiac Society (NCS) for endorsing their nomination. I know they considered me for this honor because of our relationship. Professors Sani and Karaye are prominent members of a clan that gives me joy as in them I glorify God for giving me the enablement to till the academic and professional field with the energy of youth with a bounteous harvest. They, like their colleagues, have not disappointed me.
Professor Asuquo Antia was on the faculty at the University of Ibadan in my days as a medical student. In those days, there were professors that we heard of and never saw because of their international engagements until the day of reckoning. There were those we heard of, saw, and drank from their wealth of wisdom. To my class, Prof Antia belonged to the former group. Although not readily on ground, they all strived to ensure that all products of the Ibadan Medical School were of world class; and they were passionate about this. Hence, if you met them in the examination you had to rise up to the occasion. That was my predicament when I walked into the room for my Pediatrics viva-voce examination. The younger examiner he was paired with recognized me and told him I was a serious student, introducing him in the process. That was my first encounter with him. With his awesome reputation in Pediatrics, my heart sank and I lost my composure. He then asked me a question that I should know if I was as serious as the other examiner said. And wait for it, I went “brain blocked.” He would not take the plea of the other examiner to ask me some other question. According to him and rightly so, “If I did not have answers to his question, I was not ready to become his house officer.” After what was ample time for me to give the answers, I was still tongue-tied. He stammered a bit, and while struggling to ask that I may go, the thunderbolt struck. From nowhere and as if a part of my brain was unlocked, I rattled away at the answers. He sighed and asked why I was wasting his time. Asking that I may go, I stumbled out of the room thanking God for my fortune. Those were the days. They taught passionately and examined dispassionately to uphold the system. They made us what we are. I doff my hat to all of them dead or alive.
The Kano NCS Local Organizing Committee close to the event gave the topic of this lecture to me and my consent was not sought. I am sure Professors Sani and Karaye still thought of me as that young bubbling academic of their training years who would tackle any problem flung at him. Time has however taken its toll, though I am still some way off the decline. Below however are my thoughts on the subject.
Dyslipidemia alone does not result in cardiovascular disease (CVD). It is, however, a prime factor in the development of atherosclerosis, once identified as a lipid storage disease. Atherosclerosis results in atherosclerotic CVD that takes a heavy toll on cardiac, brain, and vascular health, manifesting as coronary heart disease, heart failure, stroke, peripheral artery disease, kidney failure, blindness, and sexual dysfunction.
Dyslipidemia is one of the modifiable CVD risk factors, but its influence on CVD rates differs at different times (ages) or with gender because of certain modifying factors. For example, our arteries age with us and the changes with age make way for atherosclerosis. Regarding gender, the sex steroids determine metabolism, accumulation, and distribution of adiposity. Upper and mid-body distributions of fat superintended by male hormones are riskier.
As an identified risk factor for CVD, it is not necessarily causal albeit biologically plausible. The fact that epidemiological investigations suggest guilt only by association is what gives a foothold for vendors of a fairy tale link between dyslipidemia and CVD to stand on. However, the science is as solid as a rock, as my ancestors from antiquity know it. Where I come from, Umueleagwa Onicha Ezinihitte Mbaise in Imo State, the people have always known and say that “abuba je akposhi obi,” and people are discouraged from eating animal fat, meat preferably eaten after grilling. Translated into English literally, it means “fat locks the heart.” Do not ask me how they got to know as that would be subject of another discourse.
Atherosclerosis dates back to ancient civilization, as lesions have been found in arteries of Egyptian mummies. Obstruction of arteries by atheromatous plaques is the basis for CVD.
- Rokitansky in 1841 after 30,000 autopsies published a postulate on atheroma
- In 1858, Virchow recognized participation of cells and the proliferative nature of atheroma
- In 1933 after feeding rabbits a high cholesterol diet, Anitschkow stated that atherosclerosis was infiltrative rather than degenerative and starts with accumulation of fatty substances in the deep intima. He, however, warned that “cholesterol was not the only factor.” This is why the culprit role of cholesterol in atheroma formation has remained controversial, as several other factors need to be on hand for cholesterol to live up to its notoriety
- In 1938, Winternitz indicated that atheroma occurs partly from rupture of small capillaries of the arterial wall and that hemorrhage into the plaque and organization of this material increased the size of the atheroma. Characteristics of lipoprotein particles in the 1950s strengthened the cholesterol concept, though its culprit role in atheromata and coronary artery disease remained controversial
- Ross and Glomsett in 1976 merged the concepts of earlier investigators that atherosclerotic lesions develop only after chronic injury of the endothelial lining. The injury could be hemodynamic (turbulence), immunologic, and biochemical
- In 1986, Rose summarized pathogenesis; thus, (a) fluid dynamics in arteries creates turbulence at certain sites injuring the endothelial lining and making it permeable to lipoproteins; (b) circulating platelets clump together at these sites forming microthrombi; and (c) smooth muscles in the tunica media below proliferate under the stimulus of platelet-derived growth factor
- In 1994, Scandinavian Simvastatin Survival Study (4S) that showed a significant decrease in coronary artery disease mortality based on reduction of atherogenic index seemed to have ended the long controversy till recently when some writers tried to exculpate cholesterol from atherosclerotic CVD.
Dyslipidemia is a term used to describe blood lipid abnormalities. Lipids are hydrophobic and are transported in the blood by lipoproteins which are complex water-soluble particles that provide water-soluble transport packages. Circulating lipoproteins include high-density lipoprotein responsible for reverse transport of lipids in the blood back to the liver and reduced ability of low-density lipoprotein (LDL) to be oxidized. Others are the cholesterol-rich atherogenic Apo B lipoproteins including LDL/lipoprotein (a) which carry the bulk of cholesterol, very low-density lipoprotein and chylomicrons.
When a plaque of atheroma is cut open, it exposes a gelatinous porridge-like material containing granules of cholesterol fat, neutral fat, saturated sterols, protein granules, cholesterol crystals, fatty acids, calcium, and other cells. This porridge-like material is not in contact with flowing blood as it is covered by a hard layer of cells (fibrous tissue) but juts into the lumen of the artery. It is this hard nature of the fibrous cap that gives it the name atherosclerosis. This further deranges blood flow creating a vicious cycle. In some areas, the fibrous cap may be thin and fragile and hence prone to fracture or erosion. This is the situation in small and medium arteries. In larger caliber vessels, atheromata weaken the media and form aneurysms which contribute to CVD morbidity and mortality.
Lipids alone, as I said at the beginning, do not in isolation result in CVD. They need the endothelium to be injured first before they seize the moment. Therefore, the initial lesion is endothelial dysfunction brought on by hemodynamic or shearing consequence of hypertension. The spurt-like flow of the coronary arteries also makes them prone to hemodynamic injury. Other factors involved in endothelial dysfunction include tobacco use, especially smoking, hyperglycemia, hyperuricemia, vasculitides, alcohol abuse, obesity, and stress among others. These set up inflammation in the intima. Leukocytes are attracted and by diapedesis between the endothelial cell junctions enter the base of the intima. These sites are also permeable to oxidized lipoproteins in circulation. This is where the size of the lipoproteins matters. Here, the leukocytes (neutrophils, monocytes, and T-lymphocytes) accumulate the oxidized lipids by phagocytosis to form “foam cells.” This process is facilitated by vascular cell adhesion molecule-1 (VCAM-1). Rabbits given a normal diet do not express VCAM-1 on endothelial cells, but when fed high cholesterol diet, expression of VCAM-1 on endothelial surfaces increases. This inflammatory step in the lower intimal endothelium excites smooth muscle cells in the media to respond with proliferation. It produces monocyte chemoattractant protein-1, which assists monocyte transfer across the endothelium, further driving the process. This inflammatory process is mirrored by C-reactive protein levels. All inflammation causes injury that the body tries to counter by healing. If healing occurs completely, a hard protective cap called the plaque is formed. This juts into the lumen of the vessel creating further turbulence in flow that is adverse to endothelial function integrity. If the healing process is incomplete, the plaque is fragile and prone to fracture, rupture, or erosion. The former compromises the luminal caliber causing ischemia. With the latter, bleeding could occur as plaques contain new capillaries which could rupture with blood pressure fluxes. Exposure of raw endothelial surfaces could also attract platelets and thrombi are formed. Either way, the lumen is completely obstructed, and infarction occurs. These have been scientifically proven and that is the science.
The fairy tale as I said arose from studies plagued by confounders and selection bias. In medical literature, if you look hard enough, you can find a study that supports any idea. Recently, there was a publication titled NO SAFE LIMIT: EVEN ONE DRINK A DAY INCREASES RISK. Not long after that came a paper from Asia restating the long known truism about alcohol and health that is: all-cause mortality is worst in those that abuse alcohol followed by those who abstain before those who use sensibly and moderately.
Cholesterol is not synonymous with fat. It is a waxy chemical produced by the liver to help build cells and their outer membranes. It is also a building block of steroids and certain hormones. It is found in cheese, eggs, butter, and red fatty meat and is carried in the blood by lipoproteins. Excess cholesterol is not healthy for the heart. Cholesterol and fats/oils make up LIPIDS. The fat component of lipids could be unsaturated fat, monounsaturated fat, polyunsaturated fat, trans fat, cis fat, omega fatty acids, and saturated fat. The saturated fats are responsible for heart disease; as they increase the levels of LDL. However, if the LDL particles are large, they are not easily oxidized and hence less atherogenic. It is when the particles are small that they are easily oxidized, and given their size more easily go through the cell junctions to be phagocytosed forming “foam cells.” Association of saturated fat with health may depend on food-specific fatty acids or other nutrient constituents in foods containing the saturated fat. This is the position of de Oliveira Otto et al. in DIETARY INTAKE OF SATURATED FAT BY FOOD SOURCE AND INCIDENT CARDIOVASCULAR DISEASE: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS. Another publication calling to question the role of fat in CVD, de Souza et al deposed as follows “evidence that saturated fat are not associated with all-Cause mortality cardiovascular disease, ischaemic stroke or diabetes is heterogenous with methodological limitations.” In another breath, they state that trans fats are associated with all-cause mortality probably of higher levels of intake of industrial trans-fat than ruminant trans-fat.
A good example of this is the negative propaganda against our red palm oil. Its fat is largely saturated (approximately 50%) and explains why it solidifies at room temperature. Production method however causes different proportions of saturated and unsaturated fat; hence some remain liquid at room temperature. It is the richest source of Vitamin A in nature and being fat soluble requires fat to absorb. However, nature loaded it with antioxidants (tocotrienols and tocopherols) which ensure that after Vitamin A is extracted, the saturated fat does not attain its full oxidation potential. So you eat red palm oil and despite its proportion of saturated fat, your risk of atherosclerosis remains low, unless of course you fry the oil. This is borne out by the work of de de Oliveira Otto et al. which state that association of saturated fat with health may depend on food-specific fatty acids and other nutrient constituents.
So do not be deceived. Dyslipidemia in the right ambient would cause CVD via atherosclerosis. Even if one takes care of the modifiable risk factors, age and genetics which are non-modifiable would still put the individual in the presence of dyslipidaemia at risk for atherosclerotic CVD. Therefore, if any study excludes the right ambient, you may not see this adverse consequence. Furthermore, if a study uses food items replete with lipids but with high concentrations of antioxidants, nonoxidation of the saturated fat would not permit the development of any atherosclerotic consequence.
For me, the link is scientific and not fairy tale.
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Conflicts of interest
There are no conflicts of interest.
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