The disclosure features compositions and methods for treating cardiovascular disease by introducing one or more alterations into a lipoprotein(a) (LPA) polynucleotide in a cell. In particular embodiments, the disclosure provides a base editor system (e.g., a fusion protein or complex comprising a programable DNA binding protein, a nucleobase editor, and gRNA) for modifying an LPA polynucleotide, where the modification is associated with reduced expression, and/or reduced activity of the LPA polypeptide encoded by the polynucleotide.