Discovering FH: the medical secret of art history’s most enigmatic subject

About 1.3 million Americans have familial hypercholesterolemia (FH), a lifelong genetic condition that causes very high cholesterol levels and greatly increases the risk of cardiovascular disease. The good news is that FH is easily treatable. The bad news is that very few of those 1 million people know they have it. In fact, FH might well be one of the most obscure medical ailments that afflict large numbers of people today.

Which is why most people are surprised to learn that the signs of FH have been hiding in plain sight on one of the most famous faces in human history.

Let’s start with the medicine. Cholesterol helps our bodies build cells and protect nerves. But if too much of this waxy substance accumulates in our bloodstream — if, for instance, we’ve spent decades indulging in a diet far too rich in yummy trans fats — the resulting arterial plaque can lead to heart attacks and stroke.

Students of the medical arts have understood at least some of these basics for hundreds of years. In fact, it has been more than 500 years since Leonardo da Vinci — artist, inventor, engineer, anatomist, you name it — became first student of human anatomy to propose that the clogged arteries he discovered while dissecting older cadavers might pose a health risk.

He brought the same painstaking devotion to anatomical detail to the art for which he remains most renowned. How many times in your life have you seen pictures of Mona Lisa, the most famous painting in human history? Take a closer look: have you ever noticed that small fleshy knob at the corner of the inscrutable lady’s left eyelid?

Well, da Vinci the artist certainly noticed it while he was working on his immortal portrait of Lisa Gherardini. And da Vinci the anatomist surely would have been fascinated to learn that the FH genetic mutation, by rendering the body unable to clean LDL (“bad cholesterol”) from the bloodstream, often leads to conditions called xanthelasma (cholesterol deposits at the corner of the eyes) and xanthoma (similar deposits on the hands).

It would be hundreds of years before the medical profession understood the anatomical anomalies that da Vinci noticed in his subject (and that the Dutch painter Frans Hals painted into this 17th century portrait, and another scholar thinks might exist in a Greek statue dating to the 5th century BC). These days learning whether you’re at heightened risk for FH is as easy as ordering your kit and spitting into a little tube. It’s odd to consider just how long the clues have been there, awaiting our belated discovery. Perhaps that’s the secret behind the Mona Lisa’s enigmatic smile?