Lp(a) and Risk of Recurrent Cardiac Events in Obese Postinfarction Patients

Abstract

Studies of recurrent coronary events in obese postinfarction patients show mixed results despite potential importance of obesity‐related pathophysiologic processes and associated markers in establishing and predicting risk. The study aim was to determine specific markers of recurrent risk in obese postinfarction patients. Nondiabetic patients of the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) postinfarction study were classified according to BMI as normal weight (<25 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30 kg/m2). Cox multivariable regression with adjustment for significant clinical covariates was performed in each group monitoring outcome (cardiac death, myocardial infarction (MI), or unstable angina with 26 months follow‐up) as a function of 17 thrombogenic, inflammatory, and metabolic blood markers and 17 cardiovascular disease‐associated genetic polymorphisms. Results revealed no statistically significant genetic or blood marker variables in normal or overweight patients. For obese postinfarction patients, elevated lipoprotein(a) (Lp(a))was found to be a highly significant risk marker with hazard ratio and 95% confidence interval of 3.94 (2.11–7.35), P = 0.000017 (upper tertile vs. lower two tertiles). Additionally, elevated Lp(a) was found to interact with the −75G>A polymorphism of the apolipoprotein A‐I gene and the −250G>A polymorphism of the hepatic lipase gene in establishing risk. We conclude that interactions of elevated Lp(a) with polymorphisms of the apolipoprotein A‐I and hepatic lipase genes, primarily reflective of altered lipoprotein metabolism, play an important role in the establishment of recurrent coronary event risk in obese, nondiabetic postinfarction patients. These findings suggest close monitoring and consideration of weight reduction for obese postinfarction patients with elevated Lp(a) levels.

Lipoprotein(a) and Cardiovascular Outcomes in Patients with Previous Myocardial Infarction: A Prospective Cohort Study

“…In Ikenaga et al's retrospective study, a high Lp(a) value (≥40 mg/dL) was found to be associated with a poor prognosis after AMI in 411 patients treated with PCI 25 . Meanwhile, Lp(a) was found to be an independent predictor with HR and 95% CI of 3.94 (2.11-7.35) in 215 obese post-infarction patients during 2-year follow-up 24 . A recent observational study including 176 patients with STEMI also found a significant association of elevated Lp(a) concentrations with one-year cardiovascular outcomes 27 .…”

“…To date, Lp(a) has been suggested as a risk predictor in some special populations, such as acute coronary syndrome, stable or premature coronary artery disease (CAD), diabetes mellitus (DM), familial hypercholesterolemia (FH) or postmenopausal women [17][18][19][20][21] . Whether Lp(a) poses additional risk in patients with prior MI is still unclear and the existing studies with small sample size or short-term follow-up did not achieve consistent evidence [22][23][24][25][26][27] .…”

“…Marked differences in median plasma Lp(a) levels across studies were observed, from 12.6 mg/dL to 47 mg/dL since rate nephelometry, latex agglutination immunoassays and immunonephelometric assay were used [22][23][24][25][26] .…”

“…[17][18][19][20][21] Whether Lp(a) poses additional risk in patients with prior MI is still unclear and the existing studies with a small sample size or short-term follow-up did not achieve consistent evidence. [22][23][24][25][26][27] Based on the situation that data regarding the prognostic importance of Lp(a) in post-MI patients are limited and new therapies are in development, 12 the present study aimed to evaluate the association between Lp(a) and long-term outcomes in patients with prior MI, which may help to provide additional information concerning the future clinical application of Lp(a).…”

Importance of Endogenous Fibrinolysis in Platelet Thrombus Formation

“…It also increases synthesis of PAI-1 by endothelial cells which further reduces plasmin levels [ 16 ]. Lp(a) is also believed to be involved in atherogenesis and studies have shown links between Lp(a) levels and cardiovascular risk [ 16 , 22 , 23 , 24 ]. A summary of the regulators of fibrinolysis is provided in Table 1 .…”