The controversies from 1960s to 1980s as to whether a high blood cholesterol level is a risk factor for heart disease, were finally laid to rest in the 1990s, which saw several major clinical trials conclusively demonstrating that cholesterol reduction significantly reduces the risk of heart and blood vessel diseases.The debate then turned to defining the level of blood cholesterol at which risk increases. It becomes clear—both from long-term observations on populations and short-term clinical trials on patients—that the risk of coronary heart disease rises steadily, in a linear slope, as blood cholesterol levels rise.Progressively, the levels of total cholesterol and its dangerous sub-fraction (LDL cholesterol) that were considered acceptable (“normal”) came down and prevention thresholds as well as treatment goals were pegged at lower and lower levels as new scientific evidence came in.But fresh questions arose as to what should be the cholesterol or blood fat tests which are to be performed to best define an individual’s risk for heart disease. Obviously, these tests not only have to be accurate in predicting risk, but should also be easy to perform and relatively inexpensive.Total cholesterol levels, by themselves, predict the risk of heart attacks fairly well. However, these are two main sub-fractions of cholesterol, which have opposing effects on such risk.Low Density Lipoprotein (LDL) Cholesterol, popularly termed “bad cholesterol”, increases the risk of heart attack. High Density Lipoprotein (HDL) Cholesterol, also known as “good cholesterol”, reduces the risk of heart attack. These are respectively tagged to apolipoproteins B and A.The LDL cholesterol also exists in two major forms: the big buoyant LDL fraction and the small dense LDL fraction.The small dense LDL fraction is the most dangerous when it come to causing heart attacks and could be termed the “ugly cholesterol”.Triglycerides, another component of the blood fat pool, are also closely associated with cholesterol fractions. Elevated triglycerides usually keep company with elevated small dense LDL fraction and a reduced level of HDL cholesterol.The size of LDL particles is important, but so is their number—the more of them, greater the risk.It has been found that A to B/Apo A ratio correlates well with the abnormalities in triglycerides, HDL cholesterol as well as the number and size of LDL particles. HDL cholesterol levels, in turn, indirectly reflect the triglyceride levels and “small dense LDL” cholesterol levels.Obviously, all of these cannot be tested routinely in individuals who are being screened for risk of coronary heart disease. Tests involving triglycerides require fasting blood samples. But for total cholesterol and HDL cholesterol, one needs non-fasting blood samples.The ratio of total cholesterol to HDL cholesterol has been used as a marker of coronary risk but is not easy to communicate to lay persons.Though LDL cholesterol can be tested directly, it is usually derived from an equation that uses the levels of total cholesterol and HDL cholesterol and triglycerides (which are linked to very low density lipoproteins). Apo A and Apo B levels can be measured separately by other tests.This raises the question of what would be the best blood fat marker than can be easily measured to assess coronary riskRecently the “Inter Heart” study demonstrated that the Apo A/Apo B ratio predicted coronary risk very well across several populations in the world. However, since many laboratories do not presently perform that test routinely, we need other tests.Conventionally, total and LDL cholesterol levels have been looked at as the major risk indicators. These tests, however, do not take into account HDL cholesterol, high levels of which are protective and low levels of which predict high coronary risk.Therefore, a new marker has now emerged as the candidate for the to spot among the blood fat tests for coronary risk and can also be easily comprehended by laypersons. This is “non-HDL cholesterol”, which is obtained by simply subtracting HDL cholesterol from total cholesterol.Since both of these can be measured in non-fasting blood samples, it makes the testing even easier. This blood fat marker appears to predict coronary risk with high accuracy, as it directly or indirectly captures all of the blood fat fractions that influence coronary risk.It is suggested that persons of Indian origin should have non-HDL cholesterol levels less than 130 mg per cent to prevent heart disease. LDL cholesterol levels should be less than 100 mg per cent. HDL cholesterol levels should be more than 40 mg per cent for men and more than 50 mg per cent for women. If a person already has heart disease or diabetes, non-HDL cholesterol should be less than 100 mg per cent and LDL cholesterol should be less than 70 mg per cent. These recommendations have recently been evolved for Indians living in North-America and are also applicable to Indians living in India.It would appear that measurement of total and HDL cholesterol levels, with estimation of “non-HDL cholesterol” levels to guide prevention and treatment, would be the most cost-effective approach to the assessment of cholesterol-related coronary risk. This should be rapidly integrated into clinical practice.The writer is Professor & Head of Department of Cardiology, AIIMS
