The recent contentious American Heart Association’s guidelines on the treatment of high cholesterols, has led to a surge in articles in the literature. The basic issue? Should I treat my high cholesterol, even though I have no cardiovascular problem?
Cholesterol, triglyceride and trans-fats
Cholesterol is good, and is necessary in the body for cell membrane stability, for synthesis of hormones and vitamins, for the development of the brain and nervous system, for digestion etc. Cholesterols regulate many things from inflammation to metabolism to immune functions. But it is this same cholesterol which, in excess, blocks arteries, and which leads to a heart attack or stroke.
Cholesterol is barely soluble in water, and is transported in the blood bound to proteins called lipoproteins. There are several types of lipoproteins in the blood. In order of increasing density, they are chylomicrons, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Elevated levels of the lipoprotein fractions LDL, IDL and VLDL are regarded as atherogenic (prone to cause building up of plaque and narrowing of arteries.)
A triglyceride is an ester derived from glycerol and three fatty acids (tri + glyceride). Triglycerides are the main constituents of body fat in humans and animals, as well as vegetable fat. They are also present in the blood to enable transference of fat and blood glucose to and from the liver, and are a major component of human skin oils.
There are many different types of triglycerides, with the main division being between saturated and unsaturated types. Saturated fats are fats where the carbon atoms are "saturated" with hydrogen. These have a higher melting point and are more likely to be solid at room temperature. Unsaturated fats have double bonds between some of the carbon atoms, reducing the number of places where hydrogen atoms can bond to carbon atoms. These have a lower melting point and are more likely to be liquid at room temperature.
Trans fats (or trans fatty acids) are artificially created in an industrial process that adds hydrogen to liquid vegetable oils to make them more solid. The primary dietary source for trans fats in processed food are these "partially hydrogenated oils." Look out for them on food labels. It is this that make food tastier, last longer, and stay crisp – (biscuits, cookies, cakes, pizzas, pies, doughnuts, crackers) Trans fats are bad. Avoid it as much as possible. In November 2015 the Food and Drug Agency in the US ruled to ban it completely within three years in all processed foods that are sold.
How they are measured
Total cholesterol is defined as the sum of HDL, LDL, and VLDL. Usually, only the total cholesterol, HDL, and triglycerides are measured. For cost reasons, the VLDL is usually estimated as one-fifth of the triglycerides and the LDL is calculated using the Friedewald formula: estimated LDL = [total cholesterol] − [total HDL] − [estimated VLDL]. LDL is measured directly when triglycerides exceed 400 mg/dL because the estimated LDL and VLDL have more error when triglycerides are above 400 mg/dL.
Total Cholesterol levels, and the Cholesterol/HDL ratio levels may be a better indicator of risk of heart disease, as opposed to isolated LDL and HDL levels.To measure total cholesterol and HDL levels there is no need for fasting. Fasting is also not required for measured LDL. But if triglycerides are being checked, and the LDL calculated from that, then fasting is required.
Cholesterol is synthesized by the liver. Most ingested cholesterol is esterified, and esterified cholesterols are poorly absorbed. So cholesterol levels are not much affected by food intake. So conversely, by dieting alone, you can reduce your cholesterol levels only by about 10 percent. To reduce it further, you will need medications.
Cholesterol is recycled in the body. The liver excretes it in a non-esterified form (via bile) into the digestive tract. Typically, about 50 percent of the excreted cholesterol is reabsorbed by the small bowel back into the bloodstream.
The major difference between triglycerides and cholesterol is that triglycerides are burned to create energy while cholesterol is used to build cells and certain hormones. Cholesterol are builders inside the body. Triglycerides are broken down by the body. Both triglycerides and cholesterol are manufactured in the body; however, the body produces as much cholesterol as it needs on its own. The body relies on food consumption to make triglycerides. Triglycerides are not much of a risk factor for heart disease, unless the triglycerides are in the 500-1,000 range (normal is <150 mg/dL). Triglyceride levels require no further investigation or treatment unless the levels are above 500 mg/dL.
Indian problem, American guidelines
One thing is certain though. Indians have earlier onset, more diffuse, more severe, more extensive coronary artery disease than Westerners.
There are no data in India as to what levels of cholesterol are "high" for Indians. And many published scientific papers from India are very often not reliable. I say this with great sadness but it is true. But if you have coronary artery disease, whatever maybe your levels of cholesterol, it is high for you, and it needs treatment.
And this is where the controversy begins. Do we treat all people with high cholesterol, even if they have no symptoms?
Recently the American College of Cardiology (ACC) and the American Heart Association’s (AHA) put out their guidelines, and have recommended statin therapy for:
1. Adults with LDL of 70-189 mgm/dL and over a 7.5 percent chance of having a heart attack or stroke within 10 years ( there is a risk calculator, depending on your age, sex, and risk factors like a strong family history of heart disease, high blood pressure, diabetes, smoking, etc and is easily available online). "Family history" means a first-degree male relative below 55 yrs, or a first degree female relative below 65 years with coronary artery disease
2. Those with a previous history of a heart attack, stroke, angina, peripheral heart disease, transient ischaemic attacks, or after a CABG (or stent put into the coronaries) or other arterial revascularization procedures.
3. Those above 21 years old, with a LDL value of over 190 mgm/dL (This is the controversial aspect. Putting an asymptomatic 21-year old on statins life long is a bit excessive, in my opinion. He should try diet, exercising etc. before going on to medications.)
4. Patients with diabetes and LDL of 70-189 mgm/dl, between the ages of 40 and 75 (after that it doesn't matter, I guess.)
A look at the incidence, prevalence and relationship between heart disease and cholesterol levels, consistently reveals a log-linear relationship between them.
That means, the higher your total cholesterol, the greater your chances of heart disease. (The American Heart Association and American College of Cardiology recommend statin therapy as a Class 1 indication with level of evidence A, meaning there are multiple randomized trials to demonstrate the beneficial effects of statin therapy on prevention of cardiovascular disease and stroke).
The risk of heart attack of a stroke falls by over 20 percent for each 40 mgm reduction in LDL cholesterol. The LDL should ideally be below 100 mgm. Anything above 160 mgm is high, and should be appraised for treatment.
The statin question
The goal is not to get more people on statins. It is to reduce their risk of cardiovascular disease and stroke.
There is however, no evidence that "lower is better" as far as cholesterol levels are concerned, and there is no clear threshold levels of LDL below which coronary heart disease risk is zero. Actually there may be diminishing returns with more aggressive lowering of cholesterol levels.
There is an anti-statin lobby that feels that the entire statin industry has a lot of money, funds a lot of research, and arranges all-expenses-paid overseas conferences, gifts and holidays for cardiologists and their families. There is a strong accusation made that the whole medical fraternity has been bought over and cannot be trusted with their recommendations on statin therapy. And anti-statin advocates will say that if the cholesterol is low, you will develop everything from cancer, to dementia, to Alzheimer's disease.
Statins are extremely safe drugs, despite a small risk for muscle problems, and occasionally accelerating the development of diabetes in people with pre-diabetes. They block cholesterol synthesis in the liver. They are most effective at lowering LDL, but also have modest effects on lowering triglycerides. The beneficial effects of taking statins far outweigh its minimal side-effects. There is no of need to be afraid of statins. They are life-saving. The most commonly used ones are Atorvastatin and Rosuvastatin.
If you have high triglycerides of > 500 mg/dL, you need to take fibrates or niacin, or omega 3 fish oil supplements, in addition to statins.
There are even newer cholesterol lowering drugs like Ezetimibe (which prevents absorption of cholesterol from the intestine) and Repatha (which clears cholesterol from the liver). None of these, however, is as proven and as effective as statins.
So my advice?
If you are over 40 years, and have a risk factor (a strong family history, diabetes, hypertension, or are a smoker), and have a high cholesterol, treat it with statins. Your risk of cardiovascular disease and stroke will be significantly reduced. The evidence is overwhelming. We have been under-treating people who need statin therapy.
I believe, one day our packaged drinking water will come mixed with low-dose statins.
Disclaimer: This article is in no way sponsored by any statin manufacturer. I have no shares in any drug company. I do not take gifts from any pharmaceutical company.
(The author is a former head of the department of cardiothoracic surgery at Christian Medical College and Hospital, Vellore. He is currently the chief administrative officer, and head of the cardiothoracic surgery department at Pushpagiri Heart Institute, Tiruvalla.)