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New study casts doubts on benefits of good cholesterol for heart patients

Robin Wulffson MD's picture
HDL, LDL, good cholesterol, bad cholesterol, healthy lifestyle, genetics

High plasma HDL, also known as good cholesterol, is associated with reduced risk of heart attack.

Pharmaceutical companies are actively engaged in the development of new drugs that raise HDL. In addition, individuals with low HDL levels often receive recommendations to take medications that raise HDL as well as exercising and dieting. However, a new study published on May 16 in The Lancet raises the question of whether the association between high plasma HDL levels and heart attacks is causal.

Researchers affiliated with the Precocious Coronary Artery Disease (PROCARDIS) Consortium conducted two genetic studies known as Mendelian randomization. These studies can be used to test whether the association of a plasma biomarker (i.e., HDL) with a disease (i.e., myocardial infarction) is causal.

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The study authors stressed that they are not questioning the well-documented finding that higher HDL levels are associated with lower heart disease risk. However, they were questioning whether the relationship was causative. The first test involved the evaluation of a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser); this SNP was tested in 20 studies (20,913 myocardial infarction cases and 95,407 controls). The second genetic test involved the use of a genetic score of 14 common SNPs that exclusively associate with HDL cholesterol; this score was tested in 12,482 cases of myocardial infarction cases and 41,331 controls.

The researchers found that carriers of the LIPG 396Ser allele had higher HDL cholesterol; however, they had similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. They noted that the difference in HDL cholesterol was expected to decrease the risk of a myocardial infarction by 13%; however, they found that the 396Ser allele was not associated with a risk of myocardial infarction. From the perspective of observational epidemiology, an increase of 1 standard deviation in HDL cholesterol was associated with s reduced risk of myocardial infarction; however, a 1 standard deviation increase in HDL cholesterol due to genetic score was not associated with an increased risk of myocardial infarction (Standard deviation refers to how much variation or "dispersion" exists from the average or expected value.) For LDL cholesterol (“bad cholesterol”), the risk estimate from observational epidemiology paralleled the genetic score.

The authors concluded that some genetic factors that raise plasma HDL cholesterol do not appear to lower the risk of a myocardial infarction. They noted that their data challenges the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in the risk of a myocardial infarction.

Take home message:
This study illustrates that genetic factors are involved in the risk of a heart attack. Perhaps of more importance than focusing on a laboratory value, one should engage in a healthy life style, which includes a healthy diet and exercise program. An overweight individual with a poor diet and low physical activity is still at risk for a myocardial infarction if his or her cholesterol levels are in the normal range.

Reference: The Lancet
This page is updated on May 11, 2013.