Although a heart-healthy lifestyle is recommended for everyone, whether or not they are at risk of cardiovascular disease, this approach may not be effective for everyone.

People with two APOE e2 alleles are less likely to have elevated LDL-cholesterol, but are at an increased risk of high blood sugar, elevated triglycerides and VLDL-cholesterol and hyperlipoproteinemia type III. These people do not respond well to a low-fat diet, but a lower carbohydrate and low-sugar diet is more beneficial to maintain healthy.

Fortunately these individuals generally respond well to statins to reduce cholesterol levels if required. Individuals with one or two APOE e4 alleles are not able to metabolize fats very efficiently, so a low-fat diet is very important for people carrying this allele (whether or not they already have elevated LDL-cholesterol levels). These people tend to not respond as effectively to statin therapy, so maintaining a healthy-heart lifestyle is essential.