Cholesterol, an altered gene and the divine fruit in Limone

MEDICAL MATTERS:Making sense of good and bad cholesterol and the changed thinking on the horizon

AS AN Italophilic household, chez Houston's default location for the annual family holiday usually sees us at some end of the fascinating boot- shaped country.

This year, Lake Garda got the vote, and yet again we appreciated the quality of the food and the slow pace of Italian life.

Of course, from a health perspective, you cannot beat the Mediterranean diet. Maybe it is the holiday pace, but it seems so much easier (and cheaper!) to consume the recommended five portions of fruit and vegetables while in Italy.

The story of cholesterol and heart disease has some of its roots in the region. Limone, a small town on the lake's north-western shore, is set between high mountains. Until the construction of a lake-side road in 1932, the village was accessible only by boat. As a result, intermarriage was common; many Limonesi married close relatives, thus creating the ideal background for genetic change.

Back in 1979, a railway worker who was born in Limone, but living in Milan for over 20 years, was found to have very high cholesterol levels as part of a routine check-up. But when worried doctors checked him for heart disease and blockages in other arteries in the body, they found none. However, they did find an anomalous protein in the patient's blood, which they named Apolipoprotein A-1 Milano.

Italian physicians then went on to test the man's close relatives and discovered that his father and daughter carried the same gene. Turning to the inhabitants of Limone, doctors discovered that many local residents had the new protein in their systems. Eventually it emerged that all the present- day carriers of the altered gene are descended from a Limonese couple who married in 1644.

The anomalous protein produced by the gene mutation acts as a natural anti- cholesterol agent by efficiently transporting cholesterol to the liver, where it is broken down and eliminated from the body.

So, where do lipoproteins and the Limone discovery fit in the overall cholesterol story? Lipids, or fats, travel in the blood in combination with a protein. This lipoprotein complex contains cholesterol, triglycerides and apoprotein. Low density lipoprotein (LDL) is "bad" cholesterol; its principal protein is apolipoprotein B. The "good" cholesterol, high-density lipoprotein (HDL) contains apolipoprotein A-1.

When treating people with a cholesterol problem, doctors aim to lower a patient's LDL and increase HDL. Patients focus on keeping total fasting cholesterol and LDL below certain levels.

But now change is afoot. Studies published last month in the journal Circulation suggest that for patients already on treatment, levels of apolipoprotein B and non-HDL cholesterol are more closely associated with cardiovascular outcomes.

Co-author John La Rosa of the State University of New York said: "When you use LDL you don't take into account the intermediate density particles, things that have more triglycerides in them but still have a lot of cholesterol.

"These might not be an issue for people with very elevated LDL levels, but there are subgroups with borderline LDL levels and high triglycerides, and these people might be carrying around the intermediate particles where they still have the potential to get caught in the walls of blood vessels and cause atherosclerosis."

The latest research suggests that, in people with existing cardiovascular disease who are on treatment with statin drugs, it may be better to measure non-HDL and apo-B levels when assessing their future risk of a heart attack or stroke.

However, for those of you who have just got used to the somewhat intricate terminology surrounding LDL and HDL cholesterol, you will not be faced with additional blood measurements just yet. The authors of the latest research say that, because no interventions have been proven to reduce cardiac disease by raising HDL cholesterol or apolipoprotein A-1 levels, it is premature to introduce changes to cholesterol targets.

Meanwhile, in the absence of an injectable A-1 Milano gene, I can heartily recommend the olive oil and fruit of Limone as a painless way to reduce your risk of cardiovascular disease.

• Dr Houston is pleased to hear from readers at mhouston@irish-times.ie but regrets he is unable to reply to individual medical queries