Higher Lp(a) Indicates Greater Chance of Stenosis on CCTA in Patients With Chest Pain

Among patients with stable chest pain and suspected CAD, elevated levels of lipoprotein(a) seem to indicate a greater likelihood of finding coronary stenosis on coronary computed tomography angiography (CCTA), according to Danish registry data.

“Most patients do not go straight from [having] symptoms to invasive coronary angiography, or experience acute MI without prior symptoms, for that matter,” lead author Gitte Stokvad Brix, MD (Gødstrup Regional Hospital, Denmark), told TCTMD in an email. “As a clinician, it is crucial to identify the sick patients for referral and the non-sick ones for deferral, but there is plenty of room for improvement . . . especially in women. Thus, it is relevant to know if high (or low) levels of Lp(a) can help us in this endeavor.”

Because of all the available evidence linking Lp(a) levels with CAD risk, Brix said he was not surprised by the new results. The data support “the use of Lp(a) measurements in the diagnostic process, but it is not enough to identify the right place for Lp(a) measurements in the evaluation,” he added. “To guide the implementation of Lp(a) measurements in the evaluation of these type of patients, one must show how Lp(a) levels interact with established risk evaluation models.”

Similarly, Ron Blankstein, MD (Brigham and Women’s Hospital, Boston, MA), who commented on the findings for TCTMD, said the study “certainly adds more data to support the concept that individuals who have high lipoprotein(a) have more plaque and more stenosis, but I don’t think the results are surprising.”

While Lp(a) alone cannot explain why a patient is having chest pain, it can add to the diagnostic process, Blankstein continued. “If patients have elevated lipoprotein(a), it makes coronary CTA an even more appealing choice, because now, in addition to potentially identifying if they have atherosclerosis or stenosis, CTA will help with risk stratification for those individuals who have high Lp(a),” he said. “Conversely, when individuals are found to have atherosclerosis on CT, especially if it’s premature atherosclerosis or more plaque than would be expected, Lp(a) is helpful to better understand why it is that they have atherosclerosis.”

Lp(a) Predicts Stenosis

For the study, published online last week in the American Heart Journal, Brix and colleagues included Lp(a) and CCTA data from 4,346 patients enrolled in the Dan-NICAD study who presented with stable chest pain and suspected CAD between 2014 and 2023.

Levels of Lp(a) were considered normal (< 20 nmol/L) in just over half the population (55.6%) but moderately elevated (20 to < 125 nmol/L) in 29.4%, high (125 to < 200 nmol/L) in 9.8%, and very high (≥ 200 nmol/L) in 5.2%.

Women had higher Lp(a) levels than men, but there was no association with the biomarker and age. The lipid markers of total cholesterol, LDL cholesterol, and triglycerides also were significantly associated with Lp(a) levels, as was coronary artery calcium, even after adjustment for age, sex, body mass index, CV risk factors, and symptoms.

Overall, about one-quarter of patients (25.4%) were found to have at least one coronary stenosis on CCTA. The prevalence of both coronary stenosis as well as multivessel disease increased with Lp(a) level in this population (P < 0.001 for both).

Coronary Stenosis and Multivessel Disease Rates by Lp(a) Level

Similarly, the odds of finding stenosis increased along with Lp(a), with ORs of 1.12 (95% CI 0.96-1.31), 1.42 (1.13-1.77), and 1.67 (1.24-2.22) for patients with moderately elevated, high, and very high Lp(a), respectively, compared with normal levels. This finding did not change when the model was adjusted for age, sex, and cardiovascular risk factors.

Going forward, Brix said, “I would like to see if Lp(a) levels aid in predicting coronary stenosis beyond the information of age, sex assigned at birth, symptoms, and traditional risk factors—the characteristics included in the prediction model presently recommended by the European Society of Cardiology.” This model can already strongly predict whether a patient has coronary stenosis, but whether Lp(a) adds to it “would be interesting to know.”

‘Exciting’ Progress

Despite having been on the radar of lipidologists for more than half a century, Lp(a) has only recently come to be recognized as a valuable clinical entity and appreciated as a risk marker and potential therapeutic target, Blankstein said. Clinicians these days are more likely to be measuring it in their patients, but how to act on that continues to evolve.

In addition to outcomes trials of Lp(a)-lowering therapies, future research should, for one, address “how can we use information from imaging tests such as coronary CTA to select potential candidates for those therapies,” Blankstein added. “The second area of research is how elevated lipoprotein(a) affects plaque progression and whether that can be effectively mitigated through therapies.”

Additionally, he said: “Even in the absence of those therapies that are being developed right now, it is very important to recognize it as a risk factor, because when it is found to be elevated it should prompt treatment of all other recognizable risk factors.”