New data suggest that elevated levels of lipoprotein(a) may be associated with an increased risk for heart failure (HF) in the general population. This association was causal and mediated at least in part by coronary heart disease and aortic valve stenosis (AVS), the researchers reported.

According to study background, elevated lipoprotein(a) levels are a genetically determined risk factor for myocardial infarction (MI) and AVS. To better understand whether elevated lipoprotein(a) levels also cause HF,  the researchers assessed causality in 98 097 patients from 2 general Danish population studies, 4122 of whom had diagnosed HF.

Patients were divided into the following 5 groups based on lipoprotein(a) percentile levels: group 1 (1st-33rd percentile; <8 mg/dL); group 2 (34th-66th percentile; 8-19 mg/dL); group 3 (67th-90th percentile; 20-67 mg/dL); group 4 (91st-99th percentile; 68-153 mg/dL); and group 5 (>99th percentile; >153 mg/dL).


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When compared with group 1, the hazard ratio (HR) for HF increased as the lipoprotein(a) percentile level increased, according to multivariable adjusted analysis (P for trend <.001):

  • Group 2: HR=1.10 (95% confidence interval [CI], 0.97-1.25)
  • Group 3: HR=1.24 (95% CI, 1.08-1.42)
  • Group 4: HR=1.57 (95% CI, 1.32-1.87)
  • Group 5: HR=1.79 (95% CI, 1.18-2.73)

For elevated lipoprotein(a) levels, the population-attributable risk for HF was 9%.

In instrumental variable analysis, the combination of all LPA risk genotypes produced a genetic relative risk for HF of 1.18 (95% CI, 1.04-1.34) per tenfold higher lipoprotein(a) levels. This was similar to the corresponding observational HR of 1.22 (95% CI, 1.11-1.35), the researchers wrote.

In addition, 63% (95% CI, 45%-99%) of HF risk due to elevated lipoprotein(a) levels was mediated through MI and/or AVS.

“The implications of our findings are that lowering of lipoprotein(a) levels may potentially not only decrease risk of MI and AVS, but also, and partly by extension, decrease risk of HF,” the researchers wrote. “Our results emphasize the need for randomized clinical trials on the effect of lowering lipoprotein(a) levels to prevent cardiovascular disease. With the advent of novel lipid lowering drugs including PCSK9 inhibitors and specific apolipoprotein(a) antisense oligonucleotides with marked lipoprotein(a) lowering effects, such studies seem increasingly feasible in the near future.”

Reference

  1. Kamstrup PR, Nordestgaard BG. Elevated lipoprotein(a) levels, LPA risk genotypes, and increased risk of heart failure in the general population. JACC Heart Fail. 2015. doi:10.1016/j.jchf.2015.08.006.