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Figure Lp(a) in Chinese population
Remarks: ASO=antisense oligonucleotide, CAD=coronary artery disease, CAVS=calcification
Lp(a) is only synthesized in the liver, mainly cleared by LDL receptors in the liver, partly through the kidney and other means of removal. Lp(a) levels are usually characterized by a skewed distribution, with about 70% of people below 30 mg/dL. Among 9238 healthy people in Jiangsu Province who received
Lp(a) levels mainly depend on LPA polymorphisms (approximately 70%-90%), but some non-genetic Factors may also be related to Lp(a) levels. In patients with chronic kidney disease, serum Lp(a) levels increase with a decrease in glomerular filtration rate. In addition, serum Lp(a) levels are reduced in most patients with liver disease,
For the general population, it is recommended that everyone test the Lp(a) level at least once in their life to screen for Lp(a) Those with very high levels (≥180 mg/dL [≥430 nmol/L]). Those with extremely high levels of Lp(a) have a very high lifetime risk of ASCVD, in heterozygous familial
Genomics, epidemiology, and Mendelian randomization studies have shown that elevated levels of Lp(a) are independent risk factors for various cardiovascular diseases, Includes coronary artery disease,
The pathophysiological function of Lp(a) is not fully understood. Considering its biological structure, Lp(a) may be more likely to induce ASCVD than LDL-C. Lp(a) contains a unique protein, apo(a), which is critical for the atherogenic effect of Lp(a).
Among all lipoproteins, Lp(a) is the main carrier of OxPL. OxPL exhibits important pro-inflammatory and pro-atherogenic properties, inducing an inflammatory response in the arterial wall by activating pro-inflammatory signals in endothelial cells, smooth muscle cells, and macrophages. Due to its prothrombin and pro-inflammatory properties, Lp(a) can promote the initiation and progression of ASCVD. Recent studies have shown that Lp(a) is involved in the occurrence and development of valve and vascular calcification, but the specific mechanism is still unclear.
1. Lifestyle intervention
Diet and exercise interventions cannot directly reduce Lp(a) levels, however active control of other reversible cardiovascular risk factors is important for reducing overall cardiovascular risk in patients with elevated Lp(a) levels Risk matters. For patients with elevated Lp(a) levels and low ASCVD risk, lifestyle intervention should be encouraged. Patients with medium and high ASCVD risks are recommended to receive LDL-C lowering therapy in addition to lifestyle intervention.
2. Statins
Reducing LDL-C levels can also help reduce cardiovascular risk caused by elevated Lp(a). The 2018 ACC/AHA Cholesterol Guidelines suggest that for those with moderate ASCVD risk (10-year risk 7.5%-19.9%), Lp(a) ≥50 mg/dL or ≥100 nmol/L is a reasonable risk factor, and medium-to-high intensity may be considered Statin therapy. However, the cardiovascular risk caused by elevated Lp(a) cannot be completely eliminated by lipid-lowering drugs (such as statins) or by maintaining normal LDL-C levels.
It is recommended that for ASCVD patients with Lp(a) ≥ 30 mg/dL, statin therapy should be given until the LDL-C level Less than 55mg/dL.
3. Niacin
Niacin reduced Lp(a) levels by about 23%, but did not reduce cardiovascular risk in patients. The panel recommends further exploration of the clinical value of niacin in reducing Lp(a) levels.
4. PCSK9 inhibitor
Existing data show that monoclonal antibodies targeting PCSK9 and small interfering RNAs targeting PCSK9 messenger RNA can reduce Lp(a) levels by about 20% to 30%. For ASCVD patients with Lp(a) ≥30 mg/dL, moderate or maximum dose of statin combined
5. Lipoprotein apheresis
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After lipoprotein apheresis (LA), the level of Lp(a) can be reduced by 50%-70% immediately, with an average reduction of 30%-35% within 1 week. British
Considering the limitations of LA, the expert panel does not recommend lipoprotein apheresis as an indicator of elevated Lp(a) levels Conventional treatment. If Lp(a) ≥ 60 mg/dL, atherosclerosis is still progressively exacerbated despite sufficient LDL-C lowering targets and other risk factors are controlled, and lipoprotein apheresis can be performed.
6. New drugs under development
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RNA-targeted therapy is the intervention most likely to be approved to lower Lp(a). Antisense oligonucleotides targeting hepatic LPA RNA can silence apo(a) gene expression and block apo(a) synthesis, thereby reducing circulating Lp(a) levels. In the completed Phase I and Phase II clinical trials, antisense oligonucleotides reduced Lp(a) levels by more than 80%, and showed good safety and tolerability.
An evaluation of the antisense oligonucleotide therapy Pelacarsen (TQJ230) on cardiovascular disease in patients with elevated Lp(a) levels The global phase III HORIZON trial of outcome impact is ongoing, and this study is the first global study focusing on cardiovascular endpoints in patients with elevated Lp(a) levels. We are eager to know whether RNA-targeted therapies that lower Lp(a) actually reduce the risk of cardiovascular events.
In addition, the cholesteryl ester transfer protein inhibitor Mipomersen can reduce the plasma Lp(a) level by about 20%-30%. However, evidence to support its cardiovascular benefit is lacking.
Literature index: Jian-Jun Li, Chang-Sheng Ma, Dong Zhao, Xiao-Wei Yan, and on behalf of the on behalf of Beijing Heart Society and Expert Committee. JACC: Asia. 2022 Nov, 2 (6) 653–665.
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