Lipoprotein(a), Immune Cells and Cardiovascular Outcomes in Patients with Premature Coronary Heart Disease

Abstract

The detection of lipoprotein(a) [Lp(a)] in the artery wall at the stage of lipid-bands formation may indicate that it participates in the atherosclerosis local nonspecific inflammatory process. Innate immune cells are involved in atherogenesis, with monocytes playing a major role in the initiation of atherosclerosis, while neutrophils can contribute to plaque destabilization. This work studies the relationship between Lp(a), immune blood cells and major adverse cardiovascular events (MACE) in patients with the early manifestation of coronary heart disease (CHD). The study included 200 patients with chronic CHD, manifested up to the age of 55 in men and 60 in women. An increased Lp(a) concentration [hyperLp(a)] was shown to predict cardiovascular events in patients with premature CHD with long-term follow-up. According to the logistic regression analysis results, an increase in the monocyte count with OR = 4.58 (95% CI 1.04-20.06) or lymphocyte-to-monocyte ratio with OR = 0.82 (0.68-0.99), (p < 0.05 for both) was associated with MACE in patients with early CHD, regardless of gender, age, classical risk factors, atherogenic lipoproteins concentration and statin intake. The combination of an increased monocyte count and hyperLp(a) significantly increased the proportion of patients with early CHD with subsequent development of MACE (p = 0.02, p_trend = 0.003). The odds of cardiovascular events in patients with early CHD manifestation were highest in patients with an elevated lymphocyte-to-monocyte ratio and an elevated Lp(a) level. A higher neutrophil blood count and an elevated neutrophil-to-lymphocyte ratio determined the faster development of MACE in patients with a high Lp(a) concentration. The data obtained in this study suggest that the high atherothrombogenicity of Lp(a) is associated with the "inflammatory" component and the innate immune cells involvement in this process. Thus, the easily calculated immunological ratios of blood cells and Lp(a) concentrations can be considered simple predictors of future cardiovascular events.

Keywords: coronary heart disease; immune cells blood count; lipoprotein(a).

Figure A1

Design of the study. 260 patients with an early history of CHD hospitalized and screened between 2019 and 2021 were included during the screening phase. 60 people were expelled according to the exclusion criteria. The information about the presence or absence of any significant cardiovascular events as well as the date of each such event from the CHD manifestation was available for all patients according to medical records. All patients, after signing an informed consent, were re-examined, relevant medical data were collected, biochemical tests and routine blood tests were performed.

Figure A2

Kaplan–Meier survival curve in subgroups of patients Lp(a) < 30 mg/dL (grey solid line) and Lp(a) ≥ 30 mg/dL (black dotted line). 50% of patients in the group with elevated Lp(a) concentration lived to MACE after 96 (95% CI 60–144) months vs. 132 months (95% CI 84–192).

Figure 1

Concentration of lipoprotein(a) in patients with and without MACE. Data are presented as Box-and-Whisker plot: a grey box is drawn from the 25% and 75%; a horizontal line is a median (50%), a white square symbol is a mean, black points are values to the above of 1.5 × IQR (the Interquartile range (IQR) is calculated as 75%–25%).

Figure 2

The proportion of patients with Lp (a) ≥ 30 mg/dL in groups with and without MACE.

Figure 3

The proportion of CHD patients with and without MACE during observation period depends on blood monocyte count and Lp(a) concentration. Mon—monocytes. Median for Mon = 0.54 × 10⁹/L.

Figure 4

The proportion of CHD patients according to Lp(a) concentration, lymphocyte-to-monocyte ratio, or neutrophil-to-lymphocyte ratio in groups without (A,B) or with (C,D) MACE. LMR—lymphocyte-to-monocyte ratio, NLR—neutrophil-to-lymphocyte ratio, Me—median. Median for LMR = 4.18, for NLR = 2.66.

Figure 5

Mean survival time without MACE in subgroups of patients depending on the of Lp(a) concentration, the neutrophils blood count, or the neutrophil-to-lymphocyte ratio. NLR—neutrophil-to-lymphocyte ratio, NEU—neutrophil, Me—median. Median for NLR = 2.66, for Neu = 5.04 × 10⁹/L.

Figure 6

Kaplan–Meier survival without events curves in subgroups of patients with neutrophils count < median (A) or ≥ median (B), NLR < median (C) or ≥ median (D) depending on the of Lp(a) < 30 mg/dL (grey solid line) and Lp(a) ≥ 30 mg/dL (black dotted line). NLR—neutrophil-to-lymphocyte ratio, NEU—neutrophil, Me—median. Median for NLR 2.66, for Neu 5.04 × 10⁹/L. Sex, age of CHD manifestation, statin medication was included in model of Cox proportional regression.