Low HDL Cholesterol Common in Young MI Patients, With Young Women Faring Worse Long-Term

Young men and women who experience a first myocardial infarction are much more likely to have low HDL cholesterol levels rather than elevated LDL cholesterol levels, according to the results of a new study.

For men aged 50 years and younger who had a first MI, 72% had HDL cholesterol levels less than 40 mg/dL. In young women, 79% of those who had a first MI had HDL cholesterol levels less than 50 mg/dL.

In contrast, just 31% of men and women had LDL cholesterol greater than 130 mg/dL.    

The data, which are scheduled to be presented at the upcoming American College of Cardiology 2017 Scientific Sessions in Washington, DC, suggest that these younger patients with low HDL cholesterol levels might represent a subset of patients at an increased risk of cardiovascular events.

“I think our traditional risk calculators sort of fail these younger patients,” senior investigator Ron Blankstein, MD (Brigham and Women’s Hospital, Boston, MA), told TCTMD. “If we were to look at a young person with MI, and we were to calculate their risk score in the week before their event, the vast majority would be classified as low risk. And it’s not really that they’re low risk—they end up having events—but age is such a strong determinant of risk in most of the models we have.”

Blankstein noted that the rate of MI has steadily decreased in the United States over time, mainly through the modification of certain risk factors, such as efforts to curb smoking and to lower LDL cholesterol with increased statin use, but the decline in MI rate has not been universal. “Young individuals have not witnessed the same reduction in the rate of MI [as older patients],” he said. “Proportionally, young people are actually having more MIs than older individuals.”

Analysis of Young MI Patients at Two Major Centers

Given this background, the researchers analyzed the lipid profiles of 2,634 young men and women (≤ 50 years) who had a first MI over the past 16 years from Massachusetts General Hospital and Brigham and Women’s Hospital. The lipid panels analyzed were drawn prior to the MI or during the peri-infarction period.

I think our traditional risk calculators sort of fail these younger patients. Ron Blankstein

Overall, 944 individuals had at least one lipid abnormality, defined as either low HDL cholesterol, elevated LDL cholesterol (≥ 130 mg/dL), or elevated triglycerides (≥ 150 mg/dL). Additionally, 36% and 15% of subjects had two or all three lipid abnormalities, respectively.

The most common lipid abnormality was low HDL cholesterol levels, which was present in 74% of the entire cohort. Approximately one third of patients had elevated LDL cholesterol levels, and 48% had high triglycerides. The mean LDL cholesterol level among the men and women who had an MI was 111 mg/dL. Comparatively, the mean HDL cholesterol level was 37 mg/dL.

To TCTMD, Blankstein said that low HDL cholesterol levels should alert physicians that these particular patients might be at an increased risk of cardiovascular events. “The reality is that most people know that low HDL is a risk factor, but the magnitude of that risk factor, that importance of it, may be even greater in young individuals than if I was seeing someone older who has low HDL,” said Blankstein.

In the young patient with low HDL cholesterol, he recommends treating all modifiable risk factors. To date, researchers have not yet shown that raising HDL, either with lifestyle or various pharmacotherapies, reduces the risk of cardiovascular outcomes. In fact, several high-profile HDL-raising treatments, including two large niacin trials and multiple studies testing cholesteryl ester transfer protein (CETP) inhibition, have failed.  

“So, when somebody has low HDL, I think we have to view that patient as a high-risk patient and address not just how we are going to raise their HDL, but how we are going to improve their other risk factors, such as decreasing their LDL,” said Blankstein. “Even if their LDL is not high, if somebody is at high risk, I still want to get their LDL down. Some of these folks might be candidates for statins.”

Aside from lipid-lowering therapy, though, Blankstein said the focus should be on getting the patient to become more physically active, to lose weight, to quit smoking, to eat better, and to get their blood pressure under control. Some of these lifestyle changes can increase HDL cholesterol levels and reduce the patient’s overall risk of clinical events. “The key is we can’t just focus on HDL as our target,” he said.

To TCTMD, Michael Miller, MD (University of Maryland School of Medicine, Baltimore), noted that while HDL is an excellent biomarker of increased cardiovascular risk, he is skeptical that it is anything other than just a marker.

He pointed to a 2016 analysis of the Framingham Offspring Study, one on which he was senior author, showing that isolated low HDL cholesterol doesn’t increase cardiovascular risk unless triglyceride and LDL cholesterol levels are also elevated. Given this, like Blankstein, Miller counsels patients with low HDL cholesterol to keep other risk factors and lipids in check.    

Commenting on the study, Miller added that in the setting of an MI or during the peri-infarction period when some of the lipid levels were assessed, “HDL often plummets, [which] may help to explain the very high prevalence of low HDL.”  

Additionally, it would also be important to identify the percentage of smokers in the study since smoking, which reduces HDL cholesterol levels, is commonly observed in young MI survivors. Similarly, identifying the percentage of patients with type 2 diabetes mellitus would also be important. Both smoking status and diabetes “could have confounded the results, thereby giving the false impression that low HDL was the primary factor responsible for increased MI risk in these young patients,” said Miller.

Blankstein said the researchers are continuing to analyze the data and plan to assess dyslipidemia burden in young MI patients stratified by smoking status and other variables shortly.

Younger Women Fare Worse After MI

In addition to characterizing the burden of dyslipidemia among young patients who experience a first MI, the researchers also analyzed differences between men and women. To TCTMD, Blankstein noted that of the 2,119 patients included in this analysis, fewer women than men have an MI at younger ages. In this study, 80% of the first-MI patients were men compared with 20% of women.

Strikingly, however, after a median follow-up of 10.5 years, 15% of women had died compared with 11% of men, a statistically significant difference. In a multivariate adjusted model, which among other things adjusted for the smaller infarct size in women, female sex was associated with a 43% increased risk of all-cause mortality.

“One of the potential explanations that has been suggested in the past is that for women to have an infarct at a lower age, they have to have enough risk to overcome the protective effect of estrogen,” said Blankstein. “There’s something about these women, that because they’re having their MI at a young age, they’re at an even higher risk than their male counterparts.”

Aside from the potential that women may represent a higher-risk MI patient than men, Blankstein said further research is still needed to determine if the long-term mortality differences are the result of unmeasured confounding variables or if there are disparities in the treatment of men and women.

“There is literature pointing to the fact that women are treated less aggressively,” he said. “They are less likely to receive stents, less likely to receive some of the more aggressive medical therapies. I think it’s a fascinating question and one we want to look at—why do women do worse? Is it their inherent risk, or are they being treated differently?”