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Although physicians usually aim to lower patients' total and, in particular, LDL cholesterol, lower LDL levels are associated with developing atrial fibrillation, a study has found.

Of the nearly 16,000 participants followed for a median of 18 years, those with higher baseline levels of LDL and total cholesterol had a lower risk of incident atrial fibrillation, reported Faye L. Lopez, MS, MPH, from the University of Minnesota, and colleagues.

There was no association, however, between atrial fibrillation and baseline levels of HDL cholesterol and triglycerides, according to the study published online in Circulation: Arrhythmia and Electrophysiology.

"The inverse association of LDL cholesterol and total cholesterol with atrial fibrillation risk is intriguing, and has been previously seen in an analysis of the Cardiovascular Health Study, which included individuals ages 65 and older," Lopez and colleagues wrote.

They also noted other studies showing this inverse relationship, particularly among people with hypercholesterolemia.

However, why this relationship exists cannot be definitively answered.

One hypothesis is that subclinical hyperthyroidism might be responsible, "since hyperthyroidism reduces levels of total and LDL cholesterol, and is associated with increased risk of atrial fibrillation."

In the current study, however, researchers did not have participants' thyroid data.

Another potential reason for the inverse relationship, Lopez and colleagues said, could be the effect that blood lipids have on ion channels, which are involved in the occurrence of atrial fibrillation.

For this population-based, prospective study, researchers included 15,792 men and women ages 45 to 64 from the Atherosclerosis Risk in Communities (ARIC) study, a community-based study of cardiovascular disease in the U.S.

Initial recruitment and assessment occurred between 1987 and 1989; participants were then assessed three more times (1990-1992, 1993-1995, and 1996-1998). During follow-up, researchers recorded 1,433 new cases of atrial fibrillation.

The investigators found that higher baseline levels of LDL and total cholesterol were associated with a lower risk of atrial fibrillation.

Specifically, compared with individuals with LDL levels below 100 mg/dL, those with LDL levels between 100 mg/dL to 159 mg/dL had a 16% reduction in the risk of atrial fibrillation (HR 0.84, 95% CI 0.72 to 0.97). Those with LDL levels greater than 160 mg/dL similarly had a 15% reduced risk of atrial fibrillation (HR 0.85, 95% CI 0.72 to 1.01). The trend for both reductions approached significance at P=0.06.

For total cholesterol, those with levels at 240 mg/dL or above had a 22% reduced risk of atrial fibrillation compared with those whose total cholesterol was below 200 mg/dL (HR 0.88, 95% CI 0.76 to 1.01, P=0.03 for the trend).

The associative reduced risk of atrial fibrillation was stronger in the later visits of participants. For every one standard-deviation increment in time-varying LDL (39 mg/dL) and total cholesterol (42 mg/dL) levels, the risk of atrial fibrillation was reduced by 10% and 11% respectively, while no such reduction was seen for HDL and triglycerides.

"We don't know why there is a stronger association as participants age," senior author Alonso Alvaro, MD, PhD, told MedPage Today. "It could be that those with significantly high LDL had heart attacks and dropped out of the study, or it could be that blood lipid levels are more predictive for older rather than younger people."

Alvaro said they also could not explain why high levels of HDL did not reduce the risk of atrial fibrillation. "It could be that the mechanisms through which HDL work are not involved in the development of atrial fibrillation. But we simple do not know."

The reduced risks associated with LDL and total cholesterol levels were independent of lifestyle factors, clinical factors, and cardiovascular disease, and were similar for whites and African Americans.

Also, Lopez and colleagues did not find any independent association between lipid-lowering medications, including statins, and the risk of atrial fibrillation. This finding has more immediate clinical application, Alvaro said.

"It's another study supporting the notion that lipid-lowering medications do not reduce atrial fibrillation. I don't think we can recommend statins for the prevention of atrial fibrillation," he said, adding that the LDL and total cholesterol findings need to be validated in more studies.

A limitation to the study, noted by the authors, is that the last patient assessment occurred between 1996 and 1998, "just when statin use was gaining in popularity." They therefore could not determine how many participants with incident atrial fibrillation were receiving statins or lipid-lowering medications in the years between visit four and the year in which their atrial fibrillation occurred.

Also, most of the atrial fibrillation cases came from hospital discharge records, so there could potentially be asymptomatic cases or cases from the outpatient setting that were unaccounted for.

Lopez and colleagues also did not have information on medication dosage, nor were they able to determine the "impact of lifestyle changes patients may incorporate to become healthier after discovering they have high cholesterol."

From the American Heart Association:

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