1/5 of people have a high blood lipid index. Harvard experts explain the impact of cardiovascular health in detail

In blood lipid management, in addition to the common high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), more and more emerging evidence is prompting us not to ignore other blood lipids Indicators, one of which is lipoprotein (a) [Lp(a)]

In the latest article published in the Journal of the American Medical Association (JAMA), three experts from the Massachusetts General Hospital (MGH) of Harvard Medical School elaborated on the association between Lp(a) and cardiovascular disease risk, focusing on Lp(a) Diagnosis and treatment recommendations and the prospect of emerging therapies to reduce Lp(a) levels

What is Lp(a)

Blood lipids are the general term for cholesterol, TG and lipids (such as phospholipids) in serum

The lipid composition of Lp(a) is similar to LDL

▲The structure of Lp(a) contains Apo B, and many features are similar to LDL (picture source: reference [1])

About one-fifth of people have elevated Lp(a) levels (>50 mg/dL)

Increased Lp(a) is associated with increased cardiovascular risk

At present, there are a large number of preclinical data supporting the scientific view that "Lp(a) levels are related to cardiovascular risk", although placebo-controlled trials to test whether lowering Lp(a) levels can reduce cardiovascular risk are still ongoing In

In view of the genetic characteristics of Lp(a), Mendelian randomization method is very suitable to provide supporting evidence

The increased risk of cardiovascular disease associated with Lp(a) is mainly attributed to the dual procoagulant effects of Apo(a) and the atherosclerotic and proinflammatory effects of Apo B-related phospholipid oxidation

PCSK-9 inhibitors can reduce Lp(a) levels by approximately 25%

So, does Lp(a) level need intervention?

At present, traditional lipid testing cannot measure Lp(a) and requires a separate test, but most clinical laboratories can identify high-risk patients (>50 mg/dL[125 nmol/L])

The current American Heart Association and American College of Cardiology (AHA/ACC) guidelines recommend that Lp(a) can be used as a “risk-enhancing factor in the primary prevention of people aged 40-75 years with a 10-year ASCVD risk of 5.

The European Society of Cardiology (ESC) guidelines recommend a one-time Lp(a) measurement extensively for all adults to identify high-risk individuals—Lp(a)>180mg/dL (430 nmol/L), but this strategy is widespread The clinical impact is not yet known

At present, a consideration for whether to measure or intervene in Lp(a) is that although people with particularly high Lp(a) levels may have a life-long risk of ASCVD similar to patients with heterozygous familial hypercholesterolemia, it is clinically effective Lp(a)-lowering therapy has not been confirmed by prospective trials

Research therapies to reduce Lp(a) concentration

There are currently no approved drug therapies that can be used to reduce Lp(a) levels and related ASCVD risks

The good news is that at present, there are already new drugs that are designed to significantly reduce Lp(a) levels in the clinical development stage

Another drug, Olpasiran (Development code AMG890), a small interfering RNA (siRNA) drug targeting LPA, is currently undergoing phase 2 trials

Impact on clinical practice

Several experts concluded that: A number of evidences show that, in addition to traditional risk factors, Lp(a) levels are related to ASCVD and calcified aortic stenosis, and lowering Lp(a) concentrations may reduce these risks
.
At present, there is no strategy validated by prospective trials to solve the excessive risk related to Lp(a).
In this case, the increase of Lp(a) level may promote the comprehensive consideration of prescription statins in primary prevention, or adopt More stringent LDL-C control targets
.

In addition, because the increase in Lp(a) level may lead to inaccurate measurement results of LDL–C, for patients undergoing primary and secondary preventive treatment, it is necessary to consider subtracting Lp when assessing their LDL-C level.
(a) Level to more accurately reflect the level of LDL-C
.

Reference

[1] Miksenas H, Januzzi JL, Natarajan P.
(2021).
Lipoprotein(a) and Cardiovascular Diseases.
JAMA, DOI: 10.
1001/jama.
2021.
3632

[2] Guidelines for the Prevention and Treatment of Dyslipidemia in Adults in China (2016 Revised Edition)