Increased HDL May Not Lower Heart Attack Risk

High plasma high-density lipoprotein (HDL) cholesterol levels were not associated with a decrease in risk of myocardial infarction (MI), challenging the concept that HDL levels directly affect heart attack risk. 

Individuals carrying a single nucleotide polymorphism associated with higher plasma HDL cholesterol, in fact, had similar MI risk as other individuals.  Despite these findings, increased low-density lipoprotein (LDL) cholesterol levels were, as expected, associated with increased MI risk.

The issue in question is whether or not the relationship between high HDL levels and MI risk is causal, as previous observational studies have suggested so. 

In 4 prospective cohort studies, carriers of the HDL-increasing allele showed higher HDL levels on average by 0.14 mmol/L.  If the relationship were causal, this would have decreased the individuals’ MI risk by 13%.  But, among a total of 20,913 allele-carrying participants and 95,407 controls, higher HDL cholesterol levels were not associated with decreased MI risk. 

"These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction," researchers wrote, and "these findings emphasize the potential limitation of plasma HDL cholesterol as a surrogate measure for risk of myocardial infarction in intervention trials." 

-Michael Potts