Heart and lungs

HDL cholesterol and heart risk

“Eating lots of nuts and olive oil may be harmful for some people,” reported the Daily Mirror . The Daily Telegraph said that some heart attack patients may have genetic mutations that mean “the diet increases their risk of suffering further cardiac problems”.

The newspapers’ emphasis on the relevance of the Mediterranean diet here is misleading. The study did not look at diet and HDL levels, but attempted to define groups of people who are at higher risk of having a heart attack.

Researchers analysed the risk of heart-attack patients having a second heart attack. Those most at risk had higher overall levels of high-density lipoprotein (HDL) cholesterol and inflammatory proteins, and they also had particularly large HDL particles and some associated genetic differences.

Many previous studies have found a Mediterranean-style diet to be associated with a reduced risk of heart attack. Claiming that the opposite may be true for some people could be confusing. 

Where did the story come from?

The study was carried out by researchers, pathologists and cardiologists from the University of Rochester School of Medicine and Dentistry, and geneticists from the Southwest Foundation for Biomedical Research in Texas.

The study was supported by grants from the National Institutes of Health. It was published online in the medical journal Arteriosclerosis, Thrombosis, and Vascular Biology.

Neither the Mirror nor The Telegraph’s headlines reflect the findings of the research. The study did not look at diet, but it sought to define groups of people who are at higher risk of having a heart attack.

What kind of research was this?

This cross-sectional study in people who had already experienced a heart attack investigated how high levels of high-density lipoprotein (HDL), C-reactive protein (CRP) and other inflammatory proteins affected the risk of having a recurrent (second) heart attack.

HDL carries cholesterol away from the cells and back to the liver, where it is either broken down or passed from the body as a waste product. For this reason, it is referred to as 'good cholesterol' and, in tests, higher levels are usually considered to be better.

CRP is produced by the liver. If there is more CRP than usual, there is inflammation in your body. A CRP test can indicate inflammation in the blood stream.

The researchers also investigated the roles of other inflammatory proteins and, specifically, a protein called cholesteryl ester transfer protein (CETP) and its associated gene. This protein is involved in the regulation of cholesterol transport in and out of the proteins that carry fats around the body. The researchers say that previous research has found that some people with higher HDL cholesterol levels may actually be at higher risk of a second heart attack. This research was aimed at investigating whether CETP could be responsible for this.

The study was well conducted, and it was designed to answer the questions that the researchers set. However, the press has overstated its relevance to the diets of a general population without known heart disease and most people after a heart attack.

What did the research involve?

The researchers had data on 767 people without diabetes who had enrolled in another study of heart attacks called the THROMBO post-infarction study. Patients were enrolled after their first heart attack, and they were followed up for recurrence for over two years.

The researchers followed these people and recorded the next coronary event, such as cardiac death, heart attack or unstable angina (worsening angina pain that needs hospital admission).

They tested the patients’ blood markers two months after the first heart attack, looking for a wide range of protein types attached to cholesterol or involved in clotting and inflammation. These included ApoB, total cholesterol, lipoprotein-associated phospholipase A2, apolipoprotein A-I, HDL-C, triglyceride, glucose, insulin, lipoprotein(a), plasminogen activator inhibitor- 1, CRP, von Willebrand factor antigen, fibrinogen, D-dimer, factor VII, factor VIIa and serum amyloid A.

The researchers also separated the HDL particles according to size and sequenced the CETP gene so that they could identify which patients had one of three genotypes: B1B1, B1B2 or B2B2. CETP as a protein helps to regulate cholesterol transport in and out of the proteins that carry fats around the body.

The researchers used statistical modelling techniques to test the links between the two main blood tests, HDL and CRP, the different sized HDL molecules and the chance of carrying the CETP gene variants.

What were the basic results?

Clinical and laboratory results, including the genotyping, were available for 680 (88.7%) of the 767 patients in the study population. Average age was 58 years, 77% were men and 79% were white. In general, patients were overweight, with high triglycerides and slightly low HDL-C levels.

The researchers found they could define a subgroup of patients who had high HDL and CRP levels and who also had larger HDL particles and a higher risk of recurrence of heart attack.

In this high-risk subgroup, there was over twice the assumed risk of recurrent heart attack for those who showed less CETP activity compared with those with greater activity of this protein (hazard ratio 2.41, 95% confidence interval 1.04 to 5.60).

How did the researchers interpret the results?

The researchers say that patients with high HDL-C and C-reactive protein levels after a heart attack show increased risk for recurrent events. They say they have shown that CETP genotypic differences could be related to this increase in risk.

They call for future studies to characterise the altered HDL particles from such patients and untangle the complex physiology related to inflammation and HDL particle remodelling.


This study was designed for a different purpose to that suggested by the controversial headlines.

The researchers used a new type of data modelling to see if heart attack patients at high risk of recurrence, defined by high levels of modified HDL and CRP, could be better identified by other tests. They investigated whether a genetic test for a protein known to be involved in lipid transport could be useful in identifying high-risk patients, and found that it could.

The study had limitations, including the absence of additional risk-factor data, including diet, physical activity, alcohol consumption, blood pressure, smoking status, mental status and social support. These were not adjusted for in the results.

The main mistake in the news reporting has been the misplaced emphasis on the relevance of the Mediterranean diet to this study. The research did not look at diet or for links between food intake and HDL levels. Many previous studies have found a Mediterranean-style diet to be associated with a reduced risk of heart attack. Claiming that the opposite may be true for some people could cause unnecessary confusion.

NHS Attribution