Research evidence of Lp-PLA2 and coronary heart disease

Studies suggest that with the increase of Lp-PLA2 level, the risk of coronary heart disease and stroke increases, especially in the elderly and asymptomatic people with atherosclerotic disease. A meta-analysis of 32 prospective studies, including 79036 patients, included patients without vascular disease, stable vascular disease and acute vascular disease for 30 days. The results showed that Lp-PLA2 levels were linearly logarithmically correlated with coronary heart disease and vascular death. After adjusting for routine risk factors, the risk ratios of Lp-PLA2 level to coronary heart disease, ischemic stroke, vascular death and non vascular death were 1.11 (1.07 ~ 1.16), 1.14 (1.02 ~ 1.27), 1.13 (1.05 ~ 1.22) and 1.10 (1.03 ~ 1.18) respectively.

1. Asymptomatic high-risk population: Lp-PLA2 has different value in predicting coronary heart disease for different genders.

The nested case-control analysis of 6000 men with dyslipidemia in the WOSCOPS study showed that after adjusting for known cardiovascular risk factors and other inflammatory indicators, the RR of cardiovascular events in patients with elevated Lp-PLA2 levels was 1.18 (95% CI 1.05 ~ 1.33) [8], and the risk of coronary heart disease in patients with Lp-PLA2 levels in the highest quartile was 2-fold higher. Univariate analysis showed that CRP, leukocyte count, fibrinogen and Lp-PLA2 levels were all associated with the risk of cardiac events, but CRP and leukocyte count were only associated with events at the highest level, while different levels of Lp-PLA2 were associated with cardiac events. However, the WHS study with women as the research object found that the level of Lp-PLA2 was related to LDL-C (r = 0.51), and those receiving estrogen replacement therapy were the lowest. After adjusting for other risk factors, Lp-PLA2 levels did not predict cardiovascular events (coronary heart disease, nonfatal myocardial infarction and stroke), but hs CRP levels were associated with events. This may be related to patients receiving estrogen replacement therapy.

Lp-PLA2 level can predict the risk of coronary heart disease in healthy middle-aged people. 12819 healthy middle-aged people were selected in the ARIC study. After 6 years of follow-up, the levels of Lp-PLA2 and CRP in 608 patients with coronary heart disease events were higher than those in the control group. The hazard ratio of patients with the highest four scores of Lp-PLA2 was 1.78 [95% ci1.33 ~ 2.38]. The levels of Lp-PLA2 and CRP in patients with lower LDL-C levels (< 3.38mmol / L) were associated with coronary heart disease events, and the risk of both rising at the same time was the highest.

Lp-PLA2 is an independent predictor of coronary heart disease risk in the elderly. In the Rancho Bernardo Study, 1077 elderly community residents without a history of coronary heart disease were followed up for 16 years. Compared with the lowest quartile, the hazard ratios of higher Lp-PLA2 levels to predict the risk of coronary heart disease were 1.66, 1.80 and 1.89, respectively (P < 0.05). It is still significant after adjusting CRP and other coronary heart disease risk factors.

Since Lp-PLA2 mainly binds to LDL, lipid regulating drugs have the greatest impact on Lp-PLA2, and statins can significantly reduce the plasma level of Lp-PLA2. The prince study showed that after 12 weeks of fluvastatin treatment, the content of Lp-PLA2 in the treatment group decreased by 22.1% compared with placebo; The change of Lp-PLA2 content was moderately positively correlated with the change of LDL-C level. [11] Fenofibrate can improve HDL related Lp-PLA2. Statin treatment can affect the predictive value of Lp-PLA2. Jupiter study found that Lp-PLA2 level measured before randomized treatment was moderately correlated with LDL-C level. Lp-PLA2 level decreased by 33% and LDL-C decreased by 48.7% in rosuvastatin group. Lp-PLA2 levels were associated with cardiovascular events in patients in the placebo group, while Lp-PLA2 levels in patients in the statin treatment group did not predict the risk of cardiovascular events.

2. Stable coronary heart disease: Lp-PLA2 level can predict the risk of recurrence of cardiovascular events in patients with coronary heart disease.

3766 patients with stable coronary heart disease were enrolled in the peace study. After 4.8 years of follow-up, the incidence of composite cardiovascular events (cardiovascular death, myocardial infarction, coronary revascularization, angina hospitalization or stroke) increased significantly with the increase of Lp-PLA2 level; Lp-PLA2 level is an independent risk factor for non fatal cardiovascular events. In the study of Brilakis et al., the level of Lp-PLA2 in 504 patients undergoing coronary angiography was related to the degree of lesion [12], and the increase of Lp-PLA2 was related to the high incidence of cardiovascular events. Ludwigshafen Risk and cardiovascular health study showed that the level of Lp-PLA2 in 2454 patients with coronary heart disease confirmed by coronary angiography was highly correlated with LDL-C, apoB and non HDL-C levels, but not with hs CRP and fibrinogen. In addition, the level of Lp-PLA2 was correlated with the severity of coronary heart disease and the number of lesions. In patients not treated with statins, Lp-PLA2 levels were clearly associated with the risk of coronary heart disease.

3. Acute coronary syndrome (ACS)

Atherosclerotic plaque rupture is the main mechanism leading to acute thrombotic events, and Lp-PLA2 is an important reason for the increase of plaque vulnerability. The study of a group of patients with carotid endarterectomy showed that the level of Lp-PLA2 in carotid plaque was higher in patients with cardiovascular events. Zhu Yanzhou and others analyzed the histological characteristics of hs CRP, Lp-PLA2 and intravascular ultrasound in patients with ACS, stable coronary heart disease and non coronary heart disease. Results the levels of hs CRP and Lp-PLA2 were positively correlated with the area of atherosclerotic plaque tissue necrosis. [13] It is supported that Lp-PLA2 is an inflammatory marker of vulnerable plaque.

The correlation between Lp-PLA2 level and prognosis in patients with acute ACS is not consistent. The subgroup analysis of prove-it timi22 found that Lp-PLA2 measured 30 days after the acute phase was a prognostic index independent of LDL and CRP. A study of patients with acute myocardial infarction in the community suggests that Lp-PLA2 measured in the acute phase is associated with 1-year mortality, suggesting that Lp-PLA2 may not be affected by acute inflammatory events, but a specific indicator of vascular inflammation.

However, the follow-up analysis of two prospective studies (FRISC Ⅱ and gusto Ⅳ) from patients with acute myocardial infarction showed that although the level of Lp-PLA2 in patients with ACS was higher than that in healthy controls, it had weak correlation with known risk factors and had nothing to do with the recurrence of events in patients with ACS. Similarly, Lp-PLA2 levels measured at baseline in ACS patients enrolled in the miracle study were not associated with the primary endpoint. It was also found that atorvastatin significantly reduced the level of Lp-PLA2, and soluble PLA2 was associated with death.

NOMAS study continuously detected the changes of Lp-PLA2 level before and after myocardial infarction. Different from the rising trend of hs CRP, Lp-PLA2 level gradually decreased after the acute phase (5% per year), from the average 233 ng / ml before infarction to the average 153.9 ng / ml. Lp-PLA2 content was affected by LDL-C level. A Canadian study observed that the content of acute ACS [(143.13 ± 60.88) ng / ml] was significantly higher than that in recovery (12 weeks) [(88.74 ± 39.12) ng / ml], and the content of stable coronary heart disease [(121.72 ± 31.11) ng / ml] was also higher than that in recovery of ACS.

In conclusion, the correlation between Lp-PLA2 level and cardiovascular events in patients with ACS is not consistent, which may be related to the dynamic changes of Lp-PLA2 after ACS events. Other reasons include: different races lead to different Lp-PLA2 gene polymorphisms, different determination time windows, different determination methods, and large differences in baseline Lp-PLA2 levels in different studies.