Acute Lipoprotein (a) Reduction after PCI and the Incidence of Restenosis: a Clinical Study

Research Article

Austin Cardiol. 2021; 6(1): 1025.

Acute Lipoprotein (a) Reduction after PCI and the Incidence of Restenosis: a Clinical Study

Schulte-Hermes M¹*, Klein-Wiele O², Schulte PC³ and Seyfarth M²

¹Department of Cardiology, Pneumology and Angiology, University of Witten/Herdecke, Germany

²Department of Cardiology, University of Witten/ Herdecke, Germany

³Department of Internal Medicine III, University of Witten/Herdecke, Germany

*Corresponding author:Michael Schulte-Hermes, Department of Cardiology, Pneumology and Angiology, University of Witten/Herdecke, Prosper Hospital Recklinghausen, Germany

Received: January 28, 2021; Accepted: March 05, 2021; Published: March 12, 2021


Background: Lipoprotein (a) [Lp(a)] is a well-documented independent risk factor for Coronary Artery Disease (CAD) that also affects the lipid and coagulation systems. Nevertheless, the influence of Lp (a) on the manifestation of restenosis after Percutaneous Coronary Intervention (PCI) is not fully explored. We investigate Lp (a), fibrinogen, and plasminogen levels pre- and post-Percutaneous Coronary Intervention (PCI) to assess interaction of Lp (a) with the coagulation system.

Methods: Patients with CAD and PCI with bare metal stents were recruited between August 1998 and June 1999. Blood samples to measure Lp (a), plasminogen, and fibrinogen were taken pre-PCI, immediately after PCI, and on days one and three after PCI. Patients were followed up after six months by scheduled Coronary Angiogram (CAG).

Results: A total of 89 patients were recruited, 81 of which were examined by CAG, and 28 had restenosis after PCI (34.5%). Following PCI, patients with restenosis had a larger decrease in Lp (a) levels and fibrinogen neither of both had reached baseline by day three (Lp (a) p=0.008, fibrinogen p=0.0121).

Conclusions: From the fact that neither Lp (a), nor fibrinogen, or plasminogen had returned to baseline levels by day three after PCI, we hypothesise that there may exist a bridge between Lp (a) and the thrombosis and fibrinolysis pathways at the site of vascular injury after PCI which promotes restenosis after PCI.

Keywords: Restenosis; PCI; Lipoprotein (a); Fibrinogen; Plasminogen


Lipoprotein (a) [Lp (a)] was first described by Berg et al. in 1963 and is a risk factor for Cardiovascular Disease (CVD) although its role in promoting restenosis after Percutaneous Coronary Intervention (PCI) is still unclear. Lp (a) is an LDL-like lipoprotein with an additional Apolipoprotein (a) [apo (a)] attached to the apolipoprotein B-100 by a disulphide bridge. Plasma Lp (a) concentration is genetically determined. Levels vary widely between individuals and are not influenced by diet or exercise. The apo (a) molecule has a similar structure to that of plasminogen, thus Lp (a) can potentially reduce fibrinolysis by inhibiting the plasmin that binds to fibrin. Examination of atherosclerotic plaques have shown ingestion of Lp (a) by macrophages resulting in lipid accumulation and the building of foam cells. Another atherogenic effect of Lp (a) is reduced activation of transforming growth factor-β which inhibits cellular migration and proliferation of smooth muscle cells [1-3].

Many studies have shown elevated Lp (a) plasma levels to be an independent risk factor for CVD. Elevated Lp (a) levels have also been associated with an increased risk of major cardiac events in patients with Coronary Artery Disease (CAD) after PCI. A correlation between elevated plasma levels and incidence of restenosis was reported in one meta-analysis; however, these data remain controversial [4-6].

In the era of Bare Metal Stents (BMS), a scheduled Coronary Angiogram (CAG) was standard to detect restenosis after PCI, which occurs in about 30% of patients. Restenosis typically occurs 3 to 6 months after PCI and is defined as neointimal growth that causes a loss of more than 50% in the luminal diameter in the stent. More recently, long-term outcome after CAG with PCI has been monitored to assess a correlation between Lp (a) and CAD [7-12].

Our study aimed to ascertain the existence of a possible correlation between Lp (a) and the coagulation and fibrinolytic system with the emergence of restenosis. Most other studies focused to the absolute levels of Lp (a) before coronary interventions but the dynamic of Lp (a) changes and its correlation to the coagulation and fibrinolytic system was not investigated already.

To assess the influence of Lp (a) on the incidence of restenosis, we chose to use historic data from the BMS era because of the high incidence of restenosis at that time. The data were obtained from a study originally created to detect stent thrombosis due to high Lp (a) levels.


To search for a possible correlation between Lp (a) and the emergence of restenosis in the fibrinolytic system, we recruited 89 patients with coronary disease and single-vessel PCI with BMS between August 1998 and June 1999. Eighty-one patients were followed up with a CAG (16 females, 65 males, mean age of 63 years +/- 10.1). Blood samples werken before PCI (time A), immediately after PCI (time B) and on days one (time C) and three (time D) following PCI and prior to discharge. Blood was tested for Lp (a), plasminogen activity, and fibrinogen. Patients were followed up after 6 months and examined by scheduled CAG. CAG, PCI, and restenosis were assessed according to the European Society of Cardiology (ESC) guidelines.

The data were placed into a Microsoft Access database and documented. The statistical analyses were performed using the SPSS statistical software. Data are either presented as the mean ± SD, the median, or as counts or proportions (percentages) as appropriate. Normally distributed, continuous variables are expressed as means (±SD), while the media is given for continuous data. Categorical variables were compared using the chi-squared statistics, while the Wilcoxon test was used for continuous and ordinal variables. Significance was defined as p< 0.05.

Written concern was given from all patients. The ethic committee of the university of Bochum declared no objections to the implementation of the research project.


From the 81 patients that were followed up with CAG, 28 (34.5%) had restenosis after PCI defined as 50% stenosis in the PCI segment. Using a multivariate analysis we found no significant difference in the distribution of risk factors, such as hypertension, diabetes, hyperlipidaemia, or smoking, between patients with and without restenosis.

The median Lp (a) level before PCI (time A) was 42.74 mg/dl (±43.0). Following PCI, there was a sharp decrease in Lp (a) levels in both groups (time B) with an increase on day 1 (time C) and return to nearly normal levels on day three after PCI (time D).

To exclude the influence of heparin on LP (a) levels, we determined the Lp (a) concentration in a group of 50 patients with CAG outside the study collective after a dose of 5000IE heparin. The results yielded no change in Lp (a) levels after CAG. In the group with restenosis the Lp (a) levels were 40.4 mg/dl (±37.6) before PCI, 32.9 mg/dl (±33.1) after PCI, 33.4 mg/dl (±36.0) at day 1, and 37.9 mg/dl (±37.8) at day 3 ((Figure 1), Lp (a) levels in the restenosis group). In the group without restenosis the Lp (a) levels were 43.9 mg/dl (+45.9) before PCI, 36.0 mg/dl (±37.2) after PCI, 39.7 mg/dl (±41.1) at day 1, and 41.3 mg/dl (±43.7) at day 3 (Figure 2), Lp (a) levels in the group without restenosis).