Strengthening the reduction of LDL-C level may offset the cardiovascular risk caused by LP (a)

LP (a) is an independent risk factor for cardiovascular disease, but LP (a) is different from other lipoproteins. Improving diet and strengthening exercise cannot effectively reduce its level. In 2019, the guideline "management of dyslipidemia - lipid modification to reduce cardiovascular risk" issued by esc/eas recommended that the risk of LP (a) to patients can be reduced by strengthening the intervention of lifestyle related risk factors. However, the recommendations in the guidelines to deal with high levels of LP (a) are not clear enough. This also leads clinicians to believe that since there is no corresponding treatment for the time being, it is not necessary to detect the LP (a) level of patients. Because of this, doctors often ignore the increase of LP (a) level in patients.

Up to now, small interfering RNA (siRNA) and antisense oligonucleotide (ASO) drugs that are expected to reduce LP (a) levels are still in clinical trials and have not been approved for marketing. Is there any other way to reduce the risk of cardiovascular events caused by the high level of LP (a)?

At the European Atherosclerosis Society (EAS) conference in 2022, Brian ference, M.D., University of Cambridge, UK, shared his teams research results. The study shows that compared with the population with no increase in Lp (a), the lifetime LDL-C level of the population with high LP (a) (defined as about 120nmol/l) needs to be reduced by about 20mg/dl to offset the increased cardiovascular risk caused by the increase in Lp (a).

445765 patients from the British biological sample bank were included in this study. The inclusion criteria were: ① no ASCVD, diabetes or cancer before the age of 30; ② LDL-C level should be lower than 5mmol/l at the time of enrollment, so as to exclude patients presumed to have familial hypercholesterolemia. Based on the genetic variation related to LP (a) and LDL-C levels, patients were randomly divided into three groups - LP (a) mean level group (20nmol/l), LP (a) higher level group (123nmol/l), LP (a) higher level combined with LDL-C low level group. The primary end point of the study was the lifetime risk trajectory (age 30-80) of coronary events (fatal / nonfatal heart attack or composite events of coronary revascularization).

54% of the study participants were women, with an average age of 57.2 years at the time of enrollment. The results showed that lifetime exposure to higher levels of LP (a) was associated with a 37% increased risk of major coronary events. However, patients with higher LP (a) and lower LDL-C levels had a lower risk of coronary events. For patients with an LP (a) level of 150nmol/l, if they begin to reduce LDL-C at the age of 30, 40, 50 or 60 to offset the lifelong risk of increased LP (a), the additional LDL-C levels that need to be reduced are 0.6, 0.7, 0.9 and 1.1mmol/l, respectively. Similarly, for people with significantly increased LP (a) level, such as LP (a) level of 250nmol/l, if they begin to reduce LDL-C level at the age of 50 or 60, the additional reduced LDL-C level is 1.5 and 1.9mmol/l respectively.

Ference concluded that the later this strategy starts, the greater the reduction of LDL-C level is required. This study has strong clinical significance. It not only optimizes the absolute lifetime risk assessment of ASCVD, but also defines the strategy of strengthening the treatment of reducing LDL-C. In addition, ference believes that this study can encourage clinicians to test LP (a) levels of their patients at least once as soon as possible. Doctors identify high-risk patients with ASCVD through LP (a) test results, so as to appropriately further reduce the LDL-C level of these patients.

Ulrich laufs, M.D., University of Leipzig, Germany, agreed with ference and said that in clinical practice, physicians do not know how to manage patients with elevated LP (a) levels. This study suggests that doctors can further reduce the risk of cardiovascular disease in such patients by reducing LDL-C levels.

 

Cindy