This idea grew out of the Framingham Heart Study, the pioneering research project, started in 1948, that identified many risks for cardiovascular disease. High levels of LDL increase a person’s risk of heart attacks and strokes because it builds up in the artery walls and can cause atherosclerosis. HDL at higher levels, on the other hand, can lower overall cholesterol levels by binding to LDL and moving it to the liver, where it is excreted as waste. The ratio between a person of one type and another type matters.
But recent research shows that HDL’s story isn’t quite so simple – more Goldilocks than Jekyll and Hyde. These studies show that too little HDL is insufficient to lower LDL, but too much HDL actually increases the risk of death. The “just right” amount of HDL is between 40 and 80 mg/dL.
In a study of over 400,000 people from the general population in the UK, men with HDL levels below 40 or above 80 and women with levels above 100 were at greater risk of both all-cause and cardiovascular death in the special. There were similar findings in people who already had certain high-risk conditions. Two smaller groups of patients with coronary artery disease and HDL levels above 80 had an alarming 96 percent higher risk of overall death than those with lower HDL levels. And a study of more than 11,000 people with hypertension in Italy found a significantly higher risk of cardiovascular events in people with HDL levels below 40 and above 80.
High levels of HDL have also been shown to affect bone density. A study of more than 16,000 Australians over the age of 70 found that those with the highest HDL levels had a 33 percent greater risk of fracture than those with lower levels.
Additional disturbing evidence comes from clinical trials of drugs like niacin that attempt to raise HDL levels based on the theory that higher is better. “Those drugs have never been shown to be helpful when they were used,” along with statins, drugs that lower LDL levels, says Arshed Quyyumi, director of the Emory Clinical Cardiovascular Research Institute and co-author of two of the recent to research.
No one knows why high levels of HDL are so harmful. “That’s the million-dollar question,” says cardiologist Gaetano Santulli of Albert Einstein College of Medicine, who studies HDL. One possibility is that at higher levels, the structure of HDL molecules changes in a way that prevents them from binding tightly to circulating cholesterol to remove the excess from the blood, Santulli says. Or it could be that at very high levels, the total amount of cholesterol goes into the danger zone.
Fortunately, very high levels of HDL are found in less than 7 percent of the general population – one of the reasons the risk they carry was missed. They are more common in women but appear riskier in men, so ongoing studies are exploring the possibility that estrogen is protective.
Unfortunately, HDL levels are usually not individually controlled. They increase with exercise and moderate alcohol consumption – although heavy drinking increases total cholesterol and heart risk – but there seems to be little anyone can do to lower them if they become excessive. We therefore need to focus on keeping “bad” LDL levels low. Statins are well established as reducing cardiovascular risk. In addition, a healthy lifestyle is essential, says Monira Hussain, a chronic disease epidemiologist at Monash University in Melbourne, Australia, and co-author of the study on bone fractures. High-fiber, low-fat diets and increased exercise help lower LDL levels. Smoking is doubly harmful: it raises LDL and lowers HDL.
For their part, cardiologists need to change the way they assess their patients’ risks. “A lot of times we’re going to tell people, ‘Your HDL is sky high. You’re so protected,'” says Quyyumi. We now know that’s not true and that – like Goldilocks – we should all aim for the middle.
This is an opinion and analysis article and the views of the author or authors are not necessarily those of Scientific American.