Hidenori Arai, MD, PhD

Individuals with hypercholesterolemia who had higher levels of campesterol experienced significantly fewer cardiovascular events (CVEs), according to findings from the Kyushu Elderly Ezetimibe Phytosterol (KEEP) study that were presented at the American Heart Association Scientific Sessions 2022.

“Serum cholesterol levels depend on both cholesterol synthesis in the liver and absorption in the intestine,” the researchers wrote. “The higher absorption of cholesterol is reported to be related to a higher incidence of [CVEs].”

Hidenori Arai, MD, PhD, and colleagues hypothesized that higher cholesterol absorption markers may be associated with fewer CVEs when patients were treated with a cholesterol absorption inhibitor. Participants in the KEEP study comprised the intention-to-treat (ITT) population of the EWTOPIA75 study, which “proved the beneficial effect of ezetimibe on the prevention of CVEs in the elderly,” according to the study results.

The researchers randomly assigned 1,131 participants to a group receiving diet therapy only (diet group) and a group receiving ezetimibe (10 mg/day) plus diet therapy (ezetimibe group). Participants were followed up for 4 years. Blood samples were collected at baseline and at 24 weeks to measure serum lipids and related compounds, including cholesterol absorption and synthesis markers. Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) were also measured.

Findings Provide ‘Rationale’ for Treating Patients to Reduce CVEs

The researchers analyzed 1,061 participants from the original study cohort (501 in the ezetimibe group and 560 in the diet group). The mean age of participants was 80.5 and the female-to-male ratio was 3:2. The number of CVEs was 64.

Dr. Arai and colleagues found that increased levels of the ratio of campesterol, a cholesterol absorption marker, and campesterol/lathosterol, a cholesterol synthesis marker, at baseline were significantly associated with a decreased risk for CVEs with ezetimibe (P=0.01 and P=0.04, respectively). They reported no interaction of either lathosterol or campesterol with ezetimibe treatment on CVEs. While NT-pro BNP was significantly associated with CVE risk (P=0.004), hs-CRP was not.

The results suggest “a rationale to treat patients with higher levels of cholesterol absorption markers [with] ezetimibe, which has been proved to be effective for the prevention of CVEs,” the researchers wrote.