New insights into why humans are prone to heart attacks

The loss of a single gene two to three million years ago in our ancestors may have resulted in a heightened risk of cardiovascular disease in all humans as a species, a study suggests.

The same evolutionary gene loss may also have set up a further risk for red meat-eating humans, said researchers at University of California (UC) San Diego School of Medicine in the US.

Atherosclerosis -- the clogging of arteries with fatty deposits -- is the cause of one-third of deaths worldwide due to cardiovascular disease, they said.

There are many known risk factors, including blood cholesterol, physical inactivity, age, hypertension, obesity and smoking.

However, in roughly 15 per cent of first-time cardiovascular disease events (CVD) due to atherosclerosis, none of these factors apply.

A decade ago, researchers noted that naturally occurring coronary heart attacks due to atherosclerosis are virtually non-existent in other mammals, including closely related chimpanzees in captivity which share human-like risk factors, such as high blood lipids, hypertension and physical inactivity.

Instead, chimp "heart attacks" were due to an as-yet unexplained scarring of the heart muscle.

The new study, published in the journal PNAS, shows that mice modified to be deficient (like humans) in a sialic acid sugar molecule called Neu5Gc showed a significant increase in atherogenesis compared to control mice, who retain the CMAH gene that produces Neu5Gc.

The researchers believe a mutation that inactivated the CMAH gene occurred a few million years ago in hominin ancestors, an event possibly linked to a malarial parasite that recognised Neu5Gc.

They said human-like elimination of CMAH and Neu5Gc in mice caused an almost two-fold increase in severity of atherosclerosis compared to unmodified mice.

"The increased risk appears to be driven by multiple factors, including hyperactive white cells and a tendency to diabetes in the human-like mice," said Ajit Varki, a professor at UC San Diego.

"This may help explain why even vegetarian humans without any other obvious cardiovascular risk factors are still very prone to heart attacks and strokes, while other evolutionary relatives are not," Ajit said.

However, in consuming red meat, humans are also repeatedly exposed to Neu5Gc, which researchers said prompts an immune response and chronic inflammation they call "xenosialitis."

In their tests, human-like mice modified to lack the CMAH gene were fed a Neu5Gc-rich, high-fat diet and subsequently suffered a further 2.4-fold increase in atherosclerosis, which could not be explained by changes in blood fats or sugars.

"The human evolutionary loss of CMAH likely contributes to a predisposition to atherosclerosis by both intrinsic and extrinsic (dietary) factors, and future studies could consider using this more human-like model," Ajit said.