Higher PCSK9 levels were associated with an increased risk of mortality (HR 1.24; 95% CI 1.04-1.49; p=0.020) and the composite of mortality or heart failure hospitalization.
Observational (n=2,174)
Yes
In patients with worsening heart failure, higher PCSK9 levels and lower LDLR levels are independently associated with increased mortality and heart failure hospitalizations.
Hazard Ratio: 1.24 (95% CI 1.04–1.49)
p-value: p=0.020
BACKGROUND Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds low-density lipoprotein receptor (LDLR), preventing its recycling. PCSK9 is a risk predictor and a biotarget in atherosclerosis progression. OBJECTIVES The aim of this study was to determine whether the PCSK9-LDLR axis could predict risk in patients with heart failure (HF). METHODS The BIOSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure) is a multicenter, multinational, prospective, observational study that included patients with worsening HF signs and/or symptoms. The primary endpoints were all-cause mortality and the composite of mortality or unscheduled hospitalizations for HF. We implemented Cox proportional hazard regression to determine the simultaneously adjusted effect of PCSK9 and LDLR on both outcomes when added to the previously validated BIOSTAT-CHF risk scores. RESULTS This study included 2,174 patients (mean age: 68 ± 12 years; 53.2% had a history of ischemic heart disease). Median (interquartile range) PCSK9 and LDLR levels were 1.81 U/ml (1.45 to 2.18) and 2.98 U/ml (2.45 to 3.53), respectively. During follow-up, 569 deaths (26.2%) and 896 (41.2%) composite endpoints were ascertained. A multivariable analysis, which included BIOSTAT-CHF risk scores, LDLR, and statin treatment as covariates, revealed a positive linear association between PCSK9 levels and the risk of mortality (hazard ratio HR: 1.24; 95% confidence interval CI: 1.04 to 1.49; p = 0.020) and the composite endpoint (HR: 1.21; 95% CI: 1.05 to 1.40; p = 0.010). A similar analysis for LDLR revealed a negative association with mortality (HR: 0.86; 95% CI: 0.76 to 0.98; p = 0.025) and the composite endpoint (HR: 0.92; 95% CI: 0.83 to 1.01; p = 0.087). Including PCSK9 and LDLR improved risk score performance. CONCLUSIONS The PCSK9-LDLR axis was associated with outcomes in patients with HF. Future studies must assess whether PCSK9 inhibition will result in better outcomes in HF.
“two important questions should be investigated: whether PCSK9 inhibition in patients with WHF will lead to improved outcomes, and whether there is a cause and effect relationship between the PCSK9-LDLR axis and long-term outcomes”
Bayés‐Genís et al. (Sun,) conducted a observational in Heart failure (n=2,174). PCSK9 levels was evaluated on All-cause mortality (HR 1.24, 95% CI 1.04 to 1.49, p=0.020). Higher PCSK9 levels were associated with an increased risk of mortality (HR 1.24; 95% CI 1.04-1.49; p=0.020) and the composite of mortality or heart failure hospitalization.