Genetic predisposition to high LDL cholesterol may lead to disease in old age

By Rob Goodier

People with a genetic predisposition for high levels of low-density lipoprotein (LDL) cholesterol may be at higher risk of cardiovascular disease throughout their lives, even long into old age, a new study suggests.

The findings seem to clarify previous research suggesting that the link between high LDL cholesterol and cardiovascular disease disappears in old age, according to an article published online April 7 in the International Journal of Epidemiology.

"The study provides evidence that enhanced cholesterol carries risk throughout life and that people with enhanced risk should be properly counseled, and when necessary treated," Dr. J. Wouter Jukema, a cardiologist at Leiden University Medical Center in the Netherlands, told Reuters Health by email.

Past research has found that LDL and total cholesterol levels seem to have no link to mortality from disease after age 75, and some findings even suggest that lower total cholesterol may be linked to higher all-cause mortality in old age.

Those conclusions seem counterintuitive, so to try to cut out factors that might skew the data, Dr. Jukema and his team performed a Mendelian randomization study on genetic variations.

The researchers used data from three Dutch studies with a total of 7621 participants. They calculated each participant's genetic risk based on the number of alleles that they have that are linked to higher LDL cholesterol.

The study found that genetic risk for LDL cholesterol was indeed linked to higher LDL cholesterol levels in each age group, up to 90 years old, and those with the highest risk had the highest LDL cholesterol levels.

As age increased, however, the genetic risk for LDL cholesterol decreased.

One of the three studies included in this analysis, the Leiden Longevity Study with 3270 participants, identified people who may be predisposed toward longevity. Looking only at those people, Dr. Jukema and colleagues found that genetic longevity was linked to low risk for LDL cholesterol.

Taken together, the findings suggest that high genetic risk for LDL cholesterol is linked to heart disease and low risk may be linked to longevity, the researchers write.

"It is the expectation that this kind of (genetic) risk score makes... counseling more efficient and focused for individual patients," Dr. Jukema said.

The Netherlands Genomics Initiative/Netherlands Consortium for Healthy Ageing supported this study. The authors made no disclosures.

SOURCE: http://bit.ly/1IC5RQV

Int J Epidemiol 2015

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