CardioExchange Archive

CardioExchange, an NEJM practice community for medical professionals dedicated to improving cardiac patient care, was active from 2009 to 2015. CardioExchange fostered discussion between clinicians from across the globe.

May 17th, 2012

Study Casts Doubt on Protective Effects of Raising HDL Cholesterol

A genetics-based analysis finds that raising HDL will not necessarily lower risk for myocardial infarction. Reporting in the Lancet, researchers describe a two-pronged approach.

First, they searched for the presence of a specific allele (LIPG Asn396Ser, associated with higher HDL levels in carriers) in a large cohort of subjects with and without MI. The allele’s presence should have lowered MI risk by about 15%, but no such association was found.

Similarly, testing for the presence of an array of HDL-raising gene variants (and assigning a score on the basis of the number of variants in each subject) failed to find an association of lower risk with higher scores.

The authors conclude that raising HDL, whether with lifestyle interventions or drugs, “cannot be assumed ipso facto to lead to a corresponding benefit with respect to … myocardial infarction.”

Lancet article (Free abstract)

Lancet comment (Subscription required)

Categories: General, Prevention
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2 Responses to “Study Casts Doubt on Protective Effects of Raising HDL Cholesterol”

  1. Tariq Ahmad, MD, MPH says:
    May 17, 2012 at 12:54 pm

    This study is further proof that the relationship between HDL and myocardial infarction is a lot more nuanced than is the case with LDL.

    Nonetheless, the somewhat simplistic portrayal in the NYTimes (http://www.nytimes.com/2012/05/17/health/research/hdl-good-cholesterol-found-not-to-cut-heart-risk.html?_r=1&ref=health), may be slightly unfair.

    Could this be an example of a case where LDL’s simplicity and not HDL’s complexity is the outlier? In even many mendelian disorders, the gene-phenotype relationships are complicated (for example, Marfan and aortic disease).

    For example, a study we did (http://www.ncbi.nlm.nih.gov/pubmed/21252145?dopt=Abstract) showed that the protection from MI afforded by higher plasma levels of HDL-C may depend both on absolute levels AND variation in the genetic determinants of those levels.

    So, the benefit from HDL may depend on the path taken to get to the higher levels, as well as the genetic makeup of the patient.

    Unfortunately, we don’t know the right path yet and its probably not going to be as simple as good vs. bad cholesterol. In the meantime, there is probably no harm in telling patients with low HDL to eat right and exercise.

  2. Richard Kones, MD PhD says:
    May 18, 2012 at 9:48 am

    According to the current model of atherosclerosis pathogenesis, the “stress” upon HDL to perform (ie, to protect) arises from LDL modification within the arterial wall and subsequent retention, largely related to oxidation, glycation, carboxylation, and resulting activation of the immune system. If HDL is raised in the absence of high LDL-C levels in the absence of oxidative and immunological stress, one would expect less pathology.

    Does anyone know of a study in which HDL raised through exercise failed to improve HDL function, or produced defective HDL?

    Richard Kones MD