ABC | Volume 113, Nº2, August 2019

Original Article Yan et al. The effect of LP(a) on chronic heart failure Arq Bras Cardiol. 2019; 113(2):197-204 Clinical outcomes The median follow-up period was 186 days, with a maximum of 365 days. Clinical outcomes between groups are summarized in Table 2. The recurrent HF was significantly different between the 2 groups, but cardiac death, acute coronary syndrome, and ischemic stroke were not. The presence of elevated Lp(a) levels was associated with a greater rate of the recurrent HF (51.3% vs 78.1%, p < 0.0001). Kaplan-Meier survival analysis Kaplan-Meier survival analysis demonstrated that patients in the high Lp(a) group had a significantly higher incidence rate of the recurrent HF compared with those in the low Lp(a) group (log-rank p < 0.0001) (Figure 1). Hazard ratio (95% confidence interval) for recurrent HF events Considering Lp(a) < 20.6 as the reference group, Lp(a) ≥ 20.6 had higher risks for recurrent HF, with HR of 3.071 (95% CI, 2.283-4.130, p<0.0001). When adjusted for clinical parameters such as number of stents, multiple lesions, aldosterone antagonists, LN-NT-proBNP, SBP, NYHA class, the HR of Lp(a) ≥ 20.6 was 2.244 (95% CI, 1.493-3.371, p = 0.0001). The HR from adjusted II was further increased after further adjustment for other known confounding variables. Comparedwith the reference, the HR of Lp(a) ≥20.6 was 2.720 (95% CI, 1.730-4.277, p = 0.0001). In addition, analyses with the plasma Lp(a) levels as a continuous variable were conducted for the overall population, which showed these associations remained statistically significant after adjustment in Adjust I and Adjust II (Table 3). Discussion To our knowledge, this is the first study to analyze the association between baseline Lp(a) levels and recurrent HF in patients with chronic HF due to CHD. We found that a higher Lp(a) level is an independent predictor of the occurrence of recurrent HF in patients with chronic HF caused by CHD. Previous several studies have demonstrated the association between Lp(a) levels and cardiac and cerebrovascular events. High levels of Lp(a) are associated with increased risk of myocardial infarction in a prospective general population study with 16 years of follow-up. 8 One study revealed that Lp(a) levels at admission were independently correlated with the occurrence of MACCE in patients with STEMI. 21 Another study suggested that an elevated Lp(a) level was significantly associated with long‑term mortality following coronary angiography or percutaneous coronary intervention. 22 Although many studies have shown that LP(a) is an independent risk factor for adverse cardiac and cerebrovascular outcomes, limited data are available on the association between baseline Lp(a) levels and recurrent HF. Inourstudy,weshowedthatbaselinelevelsofLp(a)≥20.6mg/dL was associated with significantly increased risk of recurrent HF with an HR of 2.720 (95% CI, 1.730-4.277; p < 0.0001) in patients with chronic HF due to CHD during the one‑year follow‑up, even after adjustment for major covariables. This observed association is consistent with the findings from a large-scale prospective study in a Danish overall population that consisted of 98,097 participants aged 48–67 y at baseline, followed for up to 21 years (mean of 7). The population attributable risk of HF was 9% for elevated Lp(a) levels. 17 Currently, there are a few possible reasons for HF. Two possible mechanisms might explain this association between Lp(a) and HF occurrence:1) The increased HF risk due to elevated Lp(a) levels was partially mediated by myocardial infarction and/or aortic valve stenosis, 17,23 which can also be observed in our study. However, most part cannot be explained through both sides. 2) Given its proatherogenic properties, increased arterial stiffness, including vascular noncompliance in the aorta, was strongly associated with increased risk of HF. 24 Because echocardiography data were not collected, we could not assess the associations of Lp(a) levels, aortic stenosis, arterial stiffness and HF in our study. Compared with previous studies, our study included patients with a history of chronic HF. In addition, patients have poor left ventricular systolic function. The abovementioned fact is the possible cause of HF recurrence. Additionally, the median value of Lp(a) is also different among different ethnicities, such as non-Hispanic Caucasians (median, 12mg/dL [IQR, 5-32mg/dL]), and Japanese individuals (median, 13 mg/dL [IQR, 5-26 mg/dL]). 25 In our study, Lp(a) was higher than in other populations (median, 20.6 mg/dL [IQR, 12.0-35.5 mg/dL]). Apo (a) contains 10 KIV repeated Continuation Beta-blockers (%) 276 (89.3) 133 (86.4) 143 (92.3) 0.093 Aldosterone antagonists (%) 171 (55.3) 83 (53.9) 88 (56.8) 0.611 antiplatelet drugs(%) 296 (95.8) 146 (94.8) 150 (96.8) 0.389 Statins (%) 303 (98.1) 150 (97.4) 153 (98.7) 0.405 Anti-diabetic drugs(%) 125 (40.5) 55 (35.7) 70 (45.2) 0.091 AF: atrial fibrillation; ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin II receptor blocker; BMI: body mass index; DM: diabetes mellitus; eGFR: estimated glomerular filtration rate; HDL-C: high-density lipoprotein cholesterol; Lp(a): lipoprotein(a); LDL-C: low-density lipoprotein cholesterol; LVEF: left ventricular ejection fraction; LAD: lesion left anterior descending artery lesion; NYHA class: New York Heart Association class; NT-proBNP: N-terminal pro-B type natriuretic peptide; Prior MI: prior myocardial infarction; Prior CABG: prior coronary artery bypass grafting; Prior PCI: prior percutaneous coronary intervention; SBP: systolic blood pressure; TC: total cholesterol; TG: triglycerides. *LN-NT-proBNP was the natural logarithm of NT-proBNP. Data are presented as mean ± standard deviation (SD), median (interquartile range [IQR]) or n (%). 200