High levels of free fatty acid associated with sudden death

Laurent Castellucci

August 13, 2001

Mon, 13 Aug 2001 20:38:53

Paris, France - Circulating nonesterified fatty acid (NEFA) concentration is an independent risk factor for sudden death in middle-aged men who are non-ischemic, according to a study released in the August 15 issue of Circulation.

The prospective study, which followed over 5000 men for over 20 years, found that the risk of sudden death rose with concentration of NEFA, but that the risk of fatal MI did not, implying that the effect may be primarily due to proarrhythmic effects of circulating NEFA. While increased concentrations of NEFA were known to be proarrhythmic in patients with heart disease, whether or not they were dangerous for healthy men was unknown.

The study, conducted by Dr Xavier Jouven (H ô pital Europ é en Georges Pompidou) and associates, enrolled 5250 men from Paris, aged 42-53 years, between 1967 and 1972 who were free of known ischemic cardiac disease. All participants were also included in the Paris Prospective Study I and underwent a second examination 1 year after inclusion, which included measuring circulating NEFA concentration.

The men were followed for an average of 22 years, during which 1601 deaths occurred. Of these deaths, 463 were cardiovascular deaths: 91 were sudden deaths (19.7%), 145 were fatal MIs (31.3%), 22 were from cardiac failure (4.8%), 83 were from stroke (17.9%), and 37 were from other vascular causes (8.0%).

After adjusting for confounding factors (age, BMI, heart rate, systolic and diastolic blood pressure, smoking, parental history of sudden death, parental history of MI, cholesterol, triglycerides, fasting plasma glucose (or diabetic status), and insulin concentration), fasting NEFA concentration remained an independent risk factor for sudden death) but remained unassociated with death from MI.

Relative risk associated with increasing NEFA concentration*


Relative risk (95% CI)

P value

Sudden death

1.70 (1.21-2.13)

Fatal MI

0.94 (0.75-1.09)
*Increased risk is for a 1 SD increase (SD of NEFA = 144 mol/L)

The authors acknowledge that when working from death certificates, errors may creep into the diagnoses of sudden death (the working definition used was death within 1 hour of onset of acute symptoms).

Dr Alexander Leaf (Massachusetts General Hospital) points out in an accompanying editorial , that not all fatty acids are the same. He particularly points out that free fatty acids are liberated from adipose tissue at rates influenced by their molecular structure, not simply their concentration in the tissue. In addition, while the omega-6 fatty acids found in plant seed oils (corn, safflower, sunflower) have been shown to be proarrhythmic in effect, the omega-3 fatty acids (found mostly in fish) are antiarrhyhtmic. Leaf suggests that a simple dietary change, pushing the ratio of omega-3 fatty acids to omega-6 fatty acids consumed closer to 1:1, could be protective against sudden death.

Both the authors and Leaf note that because NEFA levels were associated with sudden death but not fatal MI, the potential exists for using NEFA levels in some predictive capacity. However, the researchers point out that in the study, the risk of sudden death increased concomitantly with increases in the level of circulating NEFA but with no threshold that defined high risk. This prevents NEFA measurement from being used as a simple predictor of sudden death for the individual patient in clinical practice at this time.


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